Safe administration of celecoxib to a patient with repeated episodes of nephrotic syndrome induced by NSAIDs.

Nephrotic syndrome, with or without concomitant tubulointerstitial nephritis, is a rare renal adverse effect of NSAIDs. In the present report we describe a case of a 60-year-old Caucasian man who was admitted because of nephrotic syndrome following several days of use of meloxicam for hip osteoarthritis. Renal histopathology revealed minimal change disease, one of the commonest causes of nephrotic syndrome. The patient's condition resolved rapidly upon discontinuation of meloxicam. Because he had already experienced two episodes of nephrotic syndrome after administration of diclofenac several years previously, it was concluded that the patient had renal hypersensitivity to both diclofenac and meloxicam. While waiting for the hip arthroplasty, he was prescribed celecoxib for pain control. After 1 month of regular celecoxib use the patient remained in remission with respect to nephrotic syndrome and had normal renal function. We conclude that challenge with a structurally distinct NSAID (such as celecoxib in this case) may be an option, under close surveillance, in a patient with a history of nephrotic syndrome associated with use of an NSAID when continued treatment with an NSAID is indicated.

[Tunneled dialysis catheters placement program in Clinical Hospital Merkur]. / Program postavljanja trajnih dijaliznih katetera u KB "Merkur".

INTRODUCTION: Tunneled dialysis catheters are one of the methods for vascular access in hemodialysis patients. In the Clinical Hospital Merkur placement of tunneled dialysis catheters was started in 2007. The aim of this study was to analyze results of that program. METHODS: We analyzed survival of tunneled dialysis catheters placed in our Division of nephrology from January 2009. to April 2011. First site of choice for placement of catheter was right jugular vein. Catheters were placed de novo or as over the wire exchange of a previous catheter. Catheters were placed under fluoroscopy guidance. Survival was analyzed using Kaplan-Meier analysis. Difference between survivals was tested by the log-rank test. RESULTS: 88 catheters have been placed in 70 patients. Cumulative 1- year catheter survival, censored for patient death was 58%. 1-year catheter survival analyzed by the location of placement was as follows: jugular veins 70%. right subclavian vein 58%, left subclavian vein 43% and femoral veins 33%. Left jugular vein and femoral veins had lower survival rate in comparison with jugular veins (p=0.057). There was no statistical difference in catheter survival with respect to placement de novo or after over the wire exchange (p=0,516). CONCLUSION: Jugular veins are best location for placement of tunneled dialysis catheter. There is no statistical difference of catheter survival after placement de novo or after over the wire exchange in the presence of previous catheter.

[Effect of pretransplant dialysis modality on incidence of early posttransplant infections in kidney recipients]. / Utjecaj tipa dijalize na pojavnost ranih infekcija nakon transplantacije bubrega.

INTRODUCTION: Infection is one of the main causes of patient death and graft failure early after kidney transplantation. Effect of pretransplant dialysis modality on incidence of infections after kidney transplantation still remains controversial. The aim of the present study was to determine the impact of pre-transplant dialysis modality on incidence urinary tract infections (UTI) and sepsis in early posttransplant period in kidney transplant recipients. MATERIALS AND METHODS: In this case-control retrospective study a cohort of 72 kidney, kidney- pancreas or kidney-liver transplant recipients was included. Infection was defined by either clinical presentation or microbiological finding. Infections were categorized by localization and cause of infection. In patients on peritoneal dialysis peritoneal catheter was removed intraoperatively during transplantation. Infection rate during first three months posttransplant was analyzed. Difference in frequencies was calculated using nonparametric tests. Proportions were calculated using chi2 test. Time to first infection was analyzed using Kaplan-Meier survival analysis, p value < 0.05 criterion was used to decide statistical significance. RESULTS: The total number of infections per patient per day was not significantly different in peritoneal vs. hemodialysis modality (0,029 +/- 0.019 to 0,029 +/- 0,031, p=ns). Also, there was no significant difference in peritoneal vs. hemodialysis modality in the number of UTI (0.0156 +/- 0.0144 to 0,0165 +/- 0,0125, p=ns) and sepsis (0.0018 +/- 0.0044 to 0.0026 +/- 0.0019, p=ns) during first three months posttransplant. Similarly, no difference was noted between the groups in the location or cause of infection. Peritonitis prior to transplantation was not an independent risk factor for infections (p=0.37). In Cox regression PD was not an independent risk factor for either total infections, UTI, or sepsis. CONCLUSION: This study showed that there was not statistically significant difference in the risk for infection in first three months after kidney transplantation with respect to pretransplant dialysis modality. PD should be the first choice for renal replacement therapy in patients with end stage renal disease.

Fas receptor is required for estrogen deficiency-induced bone loss in mice.

Bone mass is determined by bone cell differentiation, activity, and death, which mainly occur through apoptosis. Apoptosis can be triggered by death receptor Fas (CD95), expressed on osteoblasts and osteoclasts and may be regulated by estrogen. We have previously shown that signaling through Fas inhibits osteoblast differentiation. In this study we analyzed Fas as a possible mediator of bone loss induced by estrogen withdrawal. At 4 weeks after ovariectomy (OVX), Fas gene expression was greater in osteoblasts and lower in osteoclasts in ovariectomized C57BL/6J (wild type (wt)) mice compared with sham-operated animals. OVX was unable to induce bone loss in mice with a gene knockout for Fas (Fas -/- mice). The number of osteoclasts increased in wt mice after OVX, whereas it remained unchanged in Fas -/- mice. OVX induced greater stimulation of osteoblastogenesis in Fas -/- than in wt mice, with higher expression of osteoblast-specific genes. Direct effects on bone cell differentiation and apoptosis in vivo were confirmed in vitro, in which addition of estradiol decreased Fas expression and partially abrogated the apoptotic and differentiation-inhibitory effect of Fas in osteoblast lineage cells, while having no effect on Fas-induced apoptosis in osteoclast lineage cells. In conclusion, the Fas receptor has an important role in the pathogenesis of postmenopausal osteoporosis by mediating apoptosis and inhibiting differentiation of osteoblast lineage cells. Modulation of Fas effects on bone cells may be used as a therapeutic target in the treatment of osteoresorptive disorders.

Urine immunocytology as a noninvasive diagnostic tool for acute kidney rejection: a single center experience.

Renal biopsy is a gold standard for establishing diagnosis of acute rejection of the renal allograft. However, being invasive, renal biopsy has potential significant complications and contraindications. Therefore, possibility to noninvasively diagnose acute rejection would improve follow-up of kidney transplant patients. The purpose of this study was to evaluate urine immunocytology for T cells as a method for noninvasive identification of patients with acute renal allograft rejection in comparison to renal biopsy. In this prospective study a cohort of 56 kidney, or kidney-pancreas transplant recipients was included. Patients either received their transplant at the University Hospital "Merkur", or have been followed at the "Merkur" Hospital. Patients were subject to either protocol or indication kidney biopsy (a total of 70 biopsies), with simultaneous urine immunocytology (determination of CD3-positive cells in the urine sediment). Acute rejection was diagnosed in 24 biopsies. 23 episodes were T-cell mediated (6 grade IA, 5 grade IB, 1 grade IIA, 1 grade III and 10 borderline), while in 1 case acute humoral rejection was diagnosed. 46 biopsies did not demonstrate acute rejection. CD3-positive cells were found in 21% of cases with acute rejection and in 13% of cases without rejection (n.s.). A finding of CD3-positive cells in urine had a sensitivity of 21% and specificity of 87% for acute rejection (including borderline), with positive predictive value of 45% and negative predictive value of 68%. Although tubulitis is a hallmark of acute T cell-mediated rejection, detection of T cells in urine sediment was insufficiently sensitive and insufficiently specific for diagnosing acute rejection in our cohort of kidney transplant recipients.

Tunnelled haemodialysis catheter and haemodialysis outcomes: a retrospective cohort study in Zagreb, Croatia.

OBJECTIVES: Studies have reported that the tunnelled dialysis catheter (TDC) is associated with inferior haemodialysis (HD) patient survival, in comparison with arteriovenous fistula (AVF). Since many cofactors may also affect survival of HD patients, it is unclear whether the greater risk for survival arises from TDC per se, or from associated conditions. Therefore, the aim of this study was to determine, in a multivariate analysis, the long-term outcome of HD patients, with respect to vascular access (VA). DESIGN: Retrospective cohort study. PARTICIPANTS: This retrospective cohort study included all 156 patients with a TDC admitted at University Hospital Merkur, from 2010 to 2012. The control group consisted of 97 patients dialysed via AVF. The groups were matched according to dialysis unit and time of VA placement. The site of choice for the placement of the TDC was the right jugular vein. Kaplan-Meier analysis with log-rank test was used to assess patient survival. Multivariate Cox regression analysis was used to determine independent variables associated with patient survival. PRIMARY OUTCOME MEASURES: Patient survival with respect to VA. RESULTS: The cumulative 1-year survival of patients who were dialysed exclusively via TDC was 86.4% and of those who were dialysed exclusively via AVF, survival was 97.1% (p=0.002). In multivariate Cox regression analysis, male sex and older age were independently negatively associated with the survival of HD patients, while shorter HD vintage before the creation of the observed VA, hypertensive renal disease and glomerulonephritis were positively associated with survival. TDC was an independent risk factor for survival of HD patients (HR 23.0, 95% CI 6.2 to 85.3). CONCLUSION: TDC may be an independent negative risk factor for HD patient survival.

Effect of mycophenolate mofetil on progression of interstitial fibrosis and tubular atrophy after kidney transplantation: a retrospective study.

OBJECTIVES: Chronic transplant dysfunction after kidney transplantation is a major reason of kidney graft loss and is caused by immunological and non-immunological factors. There is evidence that mycophenolate mofetil (MMF) may exert a positive effect on renal damage in addition to immunosuppression, by its direct antifibrotic properties. The aim of our study was to retrospectively investigate the role of MMF doses on progression of chronic allograft dysfunction and fibrosis and tubular atrophy (IF/TA). SETTING: Retrospective, cohort study. PARTICIPANTS: Patients with kidney transplant in a tertiary care institution. This is a retrospective cohort study that included 79 patients with kidney and kidney-pancreas transplantation. Immunosuppression consisted of anti-interleukin 2 antibody induction, MMF, a calcineurin inhibitor±steroids. PRIMARY OUTCOME MEASURES: An association of average MMF doses over 1 year post-transplant with progression of interstitial fibrosis (Δci), tubular atrophy (Δct) and estimated-creatinine clearance (eCrcl) at 1 year post-transplant was evaluated using univariate and multivariate analyses. RESULTS: A higher average MMF dose was significantly independently associated with better eCrcl at 1 year post-transplant (b=0.21±0.1, p=0.04). In multiple regression analysis lower Δci (b=-0.2±0.09, p=0.05) and Δct (b=-0.29±0.1, p=0.02) were independently associated with a greater average MMF dose. There was no correlation between average MMF doses and incidence of acute rejection (p=0.68). CONCLUSIONS: A higher average MMF dose over 1 year is associated with better renal function and slower progression of IF/TA, at least partly independent of its immunosuppressive effects.