Mladen Knotek

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.

Combined auxiliary split liver and kidney transplantation for type I primary hyperoxaluria and end-stage kidney disease.

Primary hyperoxaluria type 1 (PH1) is a rare autosomal recessive disease, caused by loss of function in liver-specific alanine-glyoxylate aminotransferase (AGT). Accumulation of oxalate in PH1 causes nephrocalcinosis and urolithiasis leading to end-stage kidney (ESKD) in 90% of patients. These patients are treated by combined liver and kidney transplantation (LKT). Liver transplantation (LT) in PH1 has traditionally been performed as an orthotopic whole LT. Combined auxiliary LKT may mitigate the risk of whole LT, because native liver is preserved. Between 2006 and 2012 three PH1 patients with ESKD caused by nephrolithiasis received combined LKT from deceased donor at our centre (Table 1). PH1 was confirmed by genetic testing for AGT mutation. The first two patients underwent combined whole LKT, while the third one received an auxiliary LKT. Immunosuppression was conventional (daclizumab, or basiliximab induction, maintenance with tacrolimus, or cyclosporin, together with mycophenolate mofetil and steroids). Delayed graft function occurred in one of the whole LKT patients and was treated by daily dialysis. The patient subject to auxiliary LKT underwent left hepatectomy, with orthotopic transplantation of the second and third donor liver segment and KT. Immediate function of both grafts was established. However, early post-transplant daily high-flux hemodialysis was performed to enhance oxalate removal. In all three patients, function of both grafts has remained stable throughout the entire post-transplant period (Fig. 1). All patients were advised to maintain high water intake and were treated with potassium citrate and a thiazide diuretic. In the patient with auxiliary LKT, protocol biopsy at one year post-transplant demonstrated no oxalate crystal deposition in the kidney graft. The present case of a combined auxiliary LKT is, to our knowledge, only the third published case. There was no PH1 recurrence in any of them (Elias et al., Onaca et al. and our case). As it is highly unlikely that a prospective trial comparing whole liver with auxiliary LT in PH1 patients will ever be performed, publication of each such case is important. Excellent results of auxiliary LKT (Elias et al., Onaca et al. and this report), may encourage auxiliary LT in PH1 patients, prior to development of significant kidney

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.

Prognostic significance of glomerular and tubulointerstitial morphometry in idiopathic membranous nephropathy

The purpose of our study was to investigate the prognostic value of clinical and pathological, in particular glomerular and tubulointerstitial morphometric variables in idiopathic membranous nephropathy (IMN). We prospectively followed 60 Caucasian patients diagnosed with idiopathic membranous nephropathy for at least 2 years or until primary outcome (≥50% permanent decrease in estimated glomerular filtration rate or death). Glomerular and tubulointerstitial morphometric variables at the time of renal biopsy were analyzed with respect to this outcome. Univariate analysis revealed that significant negative prognostic factors for this outcome were higher cholesterol and smaller albumin concentrations, higher creatinine and maximal 24-h proteinuria, higher grade of nephroangiosclerosis, higher glomerular basement membrane thickness and glomerulopathy index, higher interstitial fibrosis and tubular atrophy percentage and higher injury score. In multivariate analysis, only the maximal 24-h proteinuria and interstitial fibrosis and tubular atrophy percentage were independent predictors of this outcome. The results suggest that morphometric analysis, mainly quantitative measurement of interstitial fibrosis and tubular atrophy percentage, injury score, glomerular basement membrane thickness and glomerulopathy index could be used as an additional method for risk stratification of patients with idiopathic membranous nephropathy.

Tacrolimus or Mycophenolate in Kidney Transplantation—Less, or More?

We have read with greatest interest a recently published paper in the American Journal of Transplantation by Bouamar et al (1). The authors reported a lack of association between the predose tacrolimus (Tac) concentration and subsequent acute rejection (AR) in kidney transplant recipients. Of note, in the Bouamar et al (1) paper, even Tac<5 ng/mL showed no associationwith an increased risk of AR, while in a multivariate analysis only the delayed graft function and induction therapy were associated with AR. While itmight be possible, as discussed by the authors, that even very low exposure to Tac may provide enough immunosuppression, there are several shortcomings of the Bouamar et al (1) paper, which make the interpretation of their results more difficult.

End-stage kidney disease after mushroom poisoning and abo-incompatible liver transplantation.

10 months after her admission, the patient is free from any sequelae of HUS. Ito et al. recently reported the efficacy of IVIG for thrombotic microangiopathy of unknown aetiology. Our patient experienced a significant and rapid improvement, especially of severe CNS signs following IVIG as well as favourable MRI changes, although the precise mechanism of this therapy remains speculative. However, we believe that both supportive therapy and anti-pro-inflammatory cytokine therapy should be considered for selected patients with HUS and CNS involvement caused by endothelial microangiopathy.

Arterial hypertension in patients undergoing hemodialysis

2017;12(3):70. 4. hrvatski kongres o hipertenziji s međunarodnim sudjelovanjem 4 Croatian Congress of Hypertension with International Participation Uvod: Arterijska hipertenzija (AH) je česta u bolesnika na hemodijalizi (HD). Etiologija je višefaktorna te je liječenje ovih bolesnika otežano. Postoje nejasnoće oko definicije, dijagnoze i prognoze AH u bolesnika na HD. Primarni cilj opservacijskog multicentričnog istraživanja je ispitati učestalost AH te antihipertenzivno liječenje u bolesnika na HD. Sekundarni cilj je usporediti rezultate s ranijim istraživanjima glede prevalencije i liječenje AH u HD bolesnika.

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.

MS340 IMMUNOSUPPRESSIVE AND ANTI-DYSLIPIDEMIC TREATMENT AFTER KIDNEY AND KIDNEY–PANCREAS TRANSPLANTATION

Hyperlipidemia is a frequent finding among renal transplant recipients. Treatment of dyslipidemias should be part of routine post-renal transplant care. Our results show a high incidence of hyperlipidemia in patients with KT and SPKT, which is in line with results from other published studies. The largest number of transplanted patients was on corticosteroid therapy. The most frequent used anti-dyslipidemic drug was fluvastatin according to the largest experience (ALERT study).