Transmission of pancreatic adenocarcinoma by a single multiorgan donor to two kidney transplant recipients: A case report.

We present two cases of transmission of a pancreatic adenocarcinoma from a single donor to two kidney transplant recipients. Autopsy of the donor revealed a pancreatic adenocarcinoma that had already spread locally to the regional lymph nodes and had not been detected at the time of organ procurement. Both recipients were carefully monitored, as neither consented to graft nephrectomy. In one patient, the tumor was discovered on surveillance biopsy of the graft approximately 14 months after transplantation, and in the second patient, ultrasound-guided aspiration needle biopsy of a growing formation in the lower pole of the graft revealed poorly differentiated metastatic adenocarcinoma. Both patients were successfully treated with graft nephrectomy and complete discontinuation of immunosuppression. None of the follow-up imaging showed persistent or recurrent malignancy, and both patients were candidates for re-transplantation. These exceptional cases of donor-derived pancreatic adenocarcinoma suggest that removal of the donor organ and restoration of immunity may lead to complete recovery.

Autologous Mesenchymal Stem Cells for Treatment of Chronic Active Antibody-Mediated Kidney Graft Rejection: Report of the Phase I/II Clinical Trial Case Series.

Mesenchymal stem cell (MSCs) therapy has already been studied in kidney transplant recipients (KTRs), and the available data showed that it is safe and well tolerated. The aim of this study was to evaluate the safety and efficacy of autologous MSCs in combination with standard therapy in KTRs with biopsy-proven chronic active antibody-mediated rejection (AMR). Patients with biopsy-proven chronic active AMR received treatment with autologous bone marrow-derived MSCs (3 × 106 cells/kg iv) after completion of standard therapy and were followed for up to 12 months. The primary endpoints were safety by assessment of adverse events. Secondary endpoints included assessment of kidney graft function, immunological and histological changes related to AMR activity and chronicity assessed by conventional microscopy and molecular transcripts. A total of 3 patients were enrolled in the study before it was terminated prematurely because of adverse events. We found that AMR did not improve in any of the patients after treatment with MSCs. In addition, serious adverse events were observed in one case when autologous MSCs therapy was administered in the late phase after kidney transplantation, which requires further elucidation.

Spot Urine Protein Excretion in the First Year Following Kidney Transplantation Associates With Allograft Rejection Phenotype at 1-Year Surveillance Biopsies: An Observational National-Cohort Study.

Introduction: Urine protein excretion is routinely measured to assess kidney allograft injury, but the diagnostic value of this measurement for kidney transplant pathology remains unclear. Here we investigated whether spot urine protein excretion in the first year following transplantation associates with allograft rejection phenotype at 1-year surveillance biopsies and de-novo occurrence of donor-specific antibodies (DSA). Patients and Methods: This prospective, observational national-cohort study included 139 non-sensitized patients who received a deceased donor kidney transplant between December 2014 and 2018. All patients received basiliximab induction and tacrolimus-based immunosuppression. Estimated protein excretion rate (ePER) was calculated monthly from spot urine protein-to-creatinine ratios. At 1-year, all recipients underwent surveillance graft biopsy and were screened for de-novo DSA. Screening-positive sera were subjected to single antigen bead (SAB) testing. The occurrence of de-novo DSA was determined based on SAB reactivity patterns using a mean fluorescence intensity threshold >1,000. Results: Among the 139 study patients, 27 patients (19%) had histologic evidence of T cell-mediated rejection (TCMR), and 9 patients (7%) had histologic evidence of antibody-mediated rejection (AMR) at 1-year surveillance biopsy. One year after transplant, 19 patients (14%) developed de-novo DSA. Compared with patients without rejection and no de-novo DSA, mixed-effects linear regression analysis showed a significant difference in slope of ePER during the first year in patients with AMR and de-novo DSA at 1-year (46, 95% CI 25-68 mg/day/1.73 m2 per month and 34, 95% CI 20-49 mg/day/1.73 m2 per month, respectively). Patients with vascular TCMR also showed a significant difference in ePER slope over time compared with patients with non-rejection findings (31, 95% CI 9-52 mg/day/1.73 m2 per month). The discriminatory power of ePER for intragraft rejection processes was better in patients with AMR (AUC 0.95, 95% CI 0.90-0.99; P < 0.001) than in those with TCMR (AUC 0.68, 95% CI 0.59-0.79; P = 0.002), with 89% sensitivity and 93% specificity for proteinuria >550 mg/day/1.73m2. Conclusions: An increase in ePER in the first year following kidney transplantation associates with AMR, vascular TCMR and de-novo DSA at 1-year and may be used as a non-invasive clinical marker of intragraft endothelial cell injury.

Glucocorticoid pathway polymorphisms and diabetes after kidney transplantation.

AIMS: To find possible associations between new-onset diabetes after transplantation and polymorphisms in glucocorticoid pathway. MATERIALS AND METHODS: A total of 290 patients from our national cohort of kidney transplant patients with functioning graft transplanted in 6 consecutive years (2010 - 2015) were included in the study. All patients were genotyped for polymorphisms in genes coding for glucocorticoid receptor (NR3C1 rs33389, rs6198 and rs33388), P-glycoprotein (ABCB1 rs1045642, rs1128503, and rs2032582), and glutathione S-transferase P1 (GSTP1 rs1695 and rs1138272). For interim analysis, clinical data were obtained from medical records for 79 patients. RESULTS: 22.8% of patients developed NODAT in the first post-transplant year. GSTP1 rs1695 and rs1138272 polymorphisms were associated with an increased risk for NODAT. NR3C1 rs6198 polymorphism was associated with higher serum glucose at the end of the first post-transplant year. CONCLUSION: The observed incidence of NODAT in the first post-transplant year is in accordance with the literature data. GSTP1 genotypes leading to decreased conjugation capacity were associated with higher probability of NODAT. As these polymorphisms can be determined already before kidney transplantation, they can help planning early glucocorticoid withdrawal if a favorable post-transplant course permits it.

Chronic hepatitis B virus infection in Slovenian national cohort of kidney transplant patients.

AIMS: To estimate the prevalence of anti-HBc-positive patients with functioning kidney graft, to detect the anti-HBc-positive patients in danger for hepatitis B virus (HBV) reactivation and to update Slovenian guidelines on hepatitis B follow-up, vaccination, introduction of chemoprophylaxis or treatment. MATERIALS AND METHODS: The Slovenian national cohort of kidney transplant patients with functioning graft managed at the University Medical Center Ljubljana was included. In a cross-sectional study between March and September 2020, all included patients were screened for the presence of anti-HBc; all anti-HBc-positive patients were additionally tested for anti-HBs, HBsAg, and HBV DNA. RESULTS: Out of a total of 778 included patients, 72 were anti-HBc positive (9.2%). Eight patients (1%) presented with asymptomatic chronic HBV infection: 6 were HBsAg-positive/HBV DNA-negative, and 2 were HBsAg-negative/HBV DNA positive. In one of the latter, HBsAg mutant variant P120QD144E was proven. By the time of the study, 12 anti-HBc-positive patients (16.6%) have already been receiving chemoprophylaxis. CONCLUSION: The prevalence of anti-HBc-positive patients in the national cohort of kidney transplant patients in Slovenia was 9.2%. Based on the specific combination of HBV markers (anti-HBc, anti-HBs, HBsAg, HBV DNA) we stratified patients into six subgroups. Algorithm on follow-up, hepatitis B vaccination, chemoprophylaxis, or treatment is presented for each of the specific subgroups.

Case Report: Capillary Leak Syndrome With Kidney Transplant Failure Following Autologous Mesenchymal Stem Cell Therapy.

Mesenchymal stem cells (MSCs) have attracted great interest in the field of kidney transplantation due to their immunomodulatory and reparative properties. In registered clinical trials, MSCs have been used before, at the time of, or early after transplantation and have been reported to be well-tolerated with no serious safety concerns. No results are available on the use of MSCs in the late post-transplant period. Here, we present a case report of a severe systemic complication mimicking capillary leak syndrome with ultimate kidney transplant failure after autologous transplantation of MSCs used as rescue treatment of late antibody-mediated kidney allograft rejection.

First and second morning spot urine protein measurements for the assessment of proteinuria: a diagnostic accuracy study in kidney transplant recipients.

BACKGROUND: Quantification of proteinuria in kidney transplant recipients is important for diagnostic and prognostic purposes. Apart from correlation tests, there have been few evaluations of spot urine protein measurements in kidney transplantation. METHODS: In this cross-sectional study involving 151 transplanted patients, we investigated measures of agreement (bias and accuracy) between the estimated protein excretion rate (ePER), determined from the protein-to-creatinine ratio in the first and second morning urine, and 24-h proteinuria and studied their performance at different levels of proteinuria. Measures of agreement were reanalyzed in relation to allograft histology in 76 patients with kidney biopsies performed for cause before enrolment in the study. RESULTS: For ePER in the first morning urine, percent bias ranged from 1 to 28% and accuracy (within 30% of 24-h collection) ranged from 56 to 73%. For the second morning urine, percent bias ranged from 2 to 11%, and accuracy ranged from 71 to 78%. The accuracy of ePER (within 30%) in first and second morning urine progressively increased from 56 and 71% for low-grade proteinuria (150-299 mg/day) to 60 and 74% for moderate proteinuria (300-999 mg/day), and to 73 and 78% for high-grade proteinuria (≥1000 mg/day). Measures of agreement were similar across histologic phenotypes of allograft injury. CONCLUSIONS: The ability of ePER to accurately predict 24-h proteinuria in kidney transplant recipients is modest. However, accuracy improves with an increase in proteinuria. Given the similar accuracy of ePER measurements in first and second morning urine, second morning urine can be used to monitor protein excretion.

Which Plant Part of Purple Coneflower (Echinacea purpurea (L.) Moench) Should be Used for Tea and Which for Tincture?

Medicinal plants are widely used for the relief of disease symptoms or as dietary supplements. In recent decades, purple coneflower has become extremely well known. An infusion or tincture of purple coneflower can be prepared by anyone simply, inexpensively, and ecologically safely. Three plant parts of purple coneflower were used in the study: extracts from roots, flowers, and leaves were obtained using three different solvents (100% and 40% ethanol and water). High-performance liquid chromatography-mass spectrophotometer identified and quantified 23 individual phenolics. Pure (100%) ethanol gave the lowest yield of all the investigated phenolic compounds in all herb parts. Chicoric and caftaric acids were the major phenolic compounds in coneflower. Caftaric acid, with health promoting properties, was extracted best in a water solution from purple coneflower leaves (2673.31 mg/100 g dry weight [DW]) and chicoric acid, also with a beneficial effect on human health, yielded the highest levels in 40% ethanol solution from flowers (1571.79 mg/100 g DW) and roots (1396.27 mg/100 g DW).

Paricalcitol versus placebo for reduction of proteinuria in kidney transplant recipients: a double-blind, randomized controlled trial.

Proteinuria after kidney transplantation is accompanied by an increased risk of graft failure. In this single-center, placebo-controlled, double-blind trial we studied whether vitamin D receptor activator paricalcitol might reduce proteinuria. Patients with urinary protein-to-creatinine ratio (UPCR) ≥20 mg/mmol despite optimization of the renin angiotensin aldosterone system (RAAS) blockade were randomly assigned to receive 24 weeks' treatment with 2 µg/day paricalcitol or placebo. Primary endpoint was change in UPCR, and main secondary endpoints were change in urinary albumin-to-creatinine ratio (UACR) and 24-h proteinuria. Analysis was by intention to treat. One hundred and sixty-eight patients undergo randomization, and 83 were allocated to paricalcitol, and 85 to placebo. Compared with baseline, UPCR declined in the paricalcitol group (-39%, 95% CI -45 to -31) but not in the placebo group (21%, 95% CI 9 to 35), with a between group difference of -49% (95% CI -57 to -41; P < 0.001). UACR and 24-h proteinuria decreased only on paricalcitol therapy and significantly differed between groups at end-of-treatment (P < 0.001). Paricalcitol was well tolerated but incidence of mild hypercalcemia was higher than in placebo. In conclusion, addition of 2 µg/day paricalcitol lowers residual proteinuria in kidney transplant recipients. Long-term studies are needed to determine if the reduction in proteinuria improves transplant outcomes (ClinicalTrials.gov, number NCT01436747).

Effects of paricalcitol on biomarkers of inflammation and fibrosis in kidney transplant recipients: results of a randomized controlled trial.

AIMS: Paricalcitol, a selective vitamin D activator, decreases proteinuria and may reduce graft failure risk in kidney transplant recipients. In this study, we evaluated the effect of paricalcitol on renin-angiotensin system (RAS) activity as well as interleukin (IL)-6 and transforming growth factor (TGF)-ß plasma concentrations as biomarkers of inflammation and fibrosis. METHODS: This placebo-controlled, double-blind trial enrolled a national cohort of kidney transplant recipients with urinary protein-to-creatinine ratio (UPCR) ≥ 20 mg/mmol despite optimization of the RAS blockade. Patients were randomly assigned to receive 24 weeks of treatment with 2 µg/day paricalcitol or placebo. The primary endpoint was the percent change in geometric mean UPCR. In this secondary analysis, we examined the effect of paricalcitol on plasma renin activity (PRA) and aldosterone levels as well as IL-6 and TGF-ß plasma concentrations from baseline to last measurement during treatment. RESULTS: Of the 168 patients with UPCR ≥ 20 mg/mmol who consented to undergoing randomization, 83 were allocated to paricalcitol and 85 to placebo. Baseline patient demographics, clinical characteristics, PRA, and aldosterone levels were similar between groups. Mean change in IL-6 was -29% (from 2.53 to 2.02 pg/mL) in the paricalcitol group and 23% (from 2.07 to 2.54 pg/mL) in the placebo group (p < 0.001). Mean change in TGF-ß was -12% (from 8,011 to 6,935 pg/mL) in the paricalcitol group and 21% (from 7,418 to 8,992 pg/mL) in the placebo group (p < 0.001). CONCLUSION: In kidney transplant recipients, the addition of 2 µg/day paricalcitol to RAS inhibition lowers IL-6 and TGF-ß concentrations, which may be beneficial for reducing graft inflammation and fibrosis.
.

Treatment of antibody-mediated rejection of kidney grafts with bortezomib and/or rituximab compared to standard regimen: experience of Slovene National Center.

BACKGROUND: The aim of our study was to determine outcomes of standard treatment of antibody-mediated rejection (ABMR) of kidney grafts as compared to the addition of bortezomib or rituximab. METHODS: The cohort of this retrospective study included patients treated for ABMR of kidney grafts at our national center in the period of 2005 - 2017, divided into two groups: standard (ST) group treated standardly with plasmapheresis or immunoadsorption, intravenous immunoglobulins, and corticosteroids, and BR group treated with the addition of bortezomib and/or rituximab. Patient and graft survival at 2 years was analyzed by Kaplan-Meier method, and predictors of graft survival were analyzed by Cox regression. RESULTS: There were 78 patients with ABMR (48 in the ST group, 30 in the BR group), 41 (53%) were men, mean age 49.5 ± 13.8 years. In ST and BR, respectively, mean serum creatinine was 267 ± 164 and 208 ± 112 µmol/L (p = 0.088), donor-specific antibodies (DSA) were positive in 75% and 97% (p = 0.022), and ABMR was acute in 50% and 33% (p = 0.149). Patient survival at 2 years was 89% in the ST and 100% in the BR group (p = 0.125). Cumulative proportion of kidney graft survival at 1 and 2 years was 67% and 53% in the ST group and 73% and 48% in the BR group, respectively, (p = 0.641). Chronic ABMR (HR 5.22, p = 0.004) was significant, while dialysis dependency at biopsy (HR 3.28, p = 0.072), serum creatinine at kidney biopsy (HR 1.003, p = 0.082), and presence of DQ-DSA (HR 3.37, p = 0.062) were borderline significant predictors of worse graft outcome. Infections were relatively common in both groups, with a trend towards more rehospitalizations due to infections in the first 6 months after treatment in the BR group (p = 0.066). In 5 patients (17%), treatment with bortezomib was discontinued prematurely due to cytopenia. CONCLUSIONS: Bortezomib or rituximab, added to standard treatment, did not significantly improve kidney graft survival and was also not associated with significant side effects, except cytopenia in some cases. Treatment of acute ABMR resulted in better graft survival than chronic ABMR.
.

Physical function and 25-hydroxyvitamin D in dialysis patients - lessons learned from the Slovenian DIAGIB study.

AIMS: Vitamin D stores in dialysis patients may be associated with their muscle function and physical performance. We analyzed associations of 25-hydroxyvitamin D levels with functional test results in prevalent hemodialysis patients and healthy controls. METHODS: Study sample included 54 dialysis patients and 81 healthy controls who performed a 6-minute walk test, sit-to-stand test, handgrip strength measurement, and self-rated habitual adjusted activity score with Human Activity Profile questionnaire. Adjusted general linear models were used to analyze association of 25-hydroxyvitamin D levels with test results. RESULTS: Serum 25-hydroxyvitamin D concentration was 73.1 ± 35.4 nmol/L in dialysis patients and 64.6 ± 22 nmol/L in controls (p = 0.12). When adjusted for age, sex, body height, spontaneous gait speed, and dialysis dependence, 25-hydroxyitamin D was significantly positively associated with 6-minute walk test result, explaining 5% of variability in walked distance (B = 0.6 m/nmol/L, p = 0.008) and 12% of variability in adjusted activity score (B = 0.1 point/nmol/L, p < 0.001). There was no significant association with handgrip strength or sit-to-stand performance in adjusted models. CONCLUSIONS: Serum 25-hydroxyvitamin D levels are significantly positively associated with submaximal aerobic physical performance and habitual activity level in dialysis patients.
.

Increase in spot urine protein excretion is associated with late kidney graft rejection and predicts rejection phenotype.

AIMS: A noninvasive test that foretells kidney graft rejection before loss of kidney function would be desirable. We hypothesized that an increase in estimated protein excretion rate (ePER) from spot urine samples is associated with graft rejection and predicts rejection phenotype. METHODS: 151 patients who had undergone first-indication kidney biopsy due to graft dysfunction beyond 3 months after transplant were identified from a national cohort of 616 transplant recipients between 2000 and 2012 (25%). ePER were calculated from spot urine protein-to-creatinine ratios at baseline, 3 months before biopsy (ePER-3m), and at the time of biopsy (ePERbiopsy) and were correlated with histologic biopsy findings. RESULTS: Levels of ePER 3 months before biopsy and at the time of biopsy were greater in 32 patients with antibody-mediated rejection (ABMR) than in 77 patients with T-cell-mediated rejection (TCMR) and 42 patients with other findings (median ePER-3m 912 vs. 320 vs. 232 mg/day/1.73m2; and median ePERbiopsy 1,672 vs. 356 vs. 268 mg/day/1.73m2; p < 0.001). Receiver operator characteristics (ROC) analyses demonstrated that ePER-3m and ePERbiopsy had good diagnostic accuracy to discriminate between biopsy specimens showing ABMR vs. those showing TCMR or other histologic findings (area under the ROC curve 0.84, 95% CI 0.75 - 0.93 and 0.89, 95% CI 0.82 - 0.97, respectively; p < 0.001). CONCLUSIONS: An increase in ePER before kidney graft dysfunction appears to be associated with graft rejection and predicts ABMR phenotype.
.

Outcome of polyomavirus nephropathy in renal transplant patients: a single-center experience.

BACKGROUND: Reduction of immunosuppression is a common therapeutic strategy in patients with polyomavirus nephropathy (PVN) but may be associated with acute rejection. This study aimed to evaluate the morphology of PVN in renal biopsies after reduction of immunosuppression. METHODS: Eight of 241 patients who received a kidney transplant between January 2012 and December 2015 presented with BK viremia and biopsy-proven PVN. Morphological evaluation according to Banff criteria and correlation with viremia and kidney function after immunosuppression reduction was performed. RESULTS: PVN grades A and B were diagnosed on average 4.7 months post-transplant in 1 and 7 patients, respectively. Indication biopsies after immunosuppression reduction showed an increase in tubulitis and interstitial inflammation score compared to those at the time of the PVN diagnosis. Surveillance biopsies 1 year after transplantation revealed resolution of interstitial inflammation and tubulitis accompanied by clearance of BK viremia in 4 patients (50%), including 1 patient with rejection. One patient showed residual interstitial inflammation after viral clearance. In these patients, renal function returned to baseline. One patient with persisting low BK virus (BKV) in serum and kidney showed a decrease of tubulointerstitial inflammation but scarring was seen. Rejection occurred in 3 patients (38%). CONCLUSION: PVN-associated interstitial inflammation and tubulitis cannot be differentiated morphologically from T-cell-mediated tubulointerstitial rejection. Significant interstitial inflammation and tubulitis in PVN under low-dose immunosuppression might represent immune reconstitution injury, which is reduced after successful BKV clearance from the serum and kidney. Concomitant rejection in PVN patients on low immunosuppression might be efficiently treated with transient pulse immunosuppressive therapy.
.

The role of single nucleotide polymorphisms of CYP3A and ABCB1 on tacrolimus predose concentration in kidney transplant recipients.

BACKGROUND: Tacrolimus has a narrow therapeutic drug window but high inter- and intrapatient variability. Our aim is to construct a model able to predict optimal maintenance tacrolimus predose concentration (C0) in kidney transplant patients. Here we present our study design and genotype and variant allele frequencies for the selected single nucleotide polymorphisms of genes involved in tacrolimus metabolism in our national cohort of kidney transplant recipients. METHODS: In the observational part of the study, we intend to determine allelic variants of CYP3A4, CYP3A5, and ABCB1 gene in a national cohort of 700 kidney transplants recipients. Clinical and laboratory data of this historic cohort will be added to assess patient's immunologic risk. Based on these data, a prediction model will be constructed that will be validated in a prospective randomized study in 60 de-novo kidney transplant recipients. RESULTS: Our interim cross-sectional observational results show higher variability of ABCB1 genotypes when compared to CYP3A genes, with more than two thirds of the population carrying at least one polymorphic allele. On the other hand, less than 1% of our transplant recipients possess the CYP3A genotype, which requires high daily tacrolimus dose. CONCLUSIONS: Due to high inter- and intrapatient tacrolimus variability, a patient-tailored approach to define the optimal maintenance tacrolimus C0 for each individual patient is needed. Our model will rely on individual pharmacogenomic and clinical data to cover different patient-specific risk factors for adverse outcomes.
.

Acute granulomatous interstitial nephritis and acute rejection in a kidney transplant recipient after zoledronic acid therapy - a case report and review of the literature.

BACKGROUND: Acute granulomatous interstitial nephritis (AGIN) in native kidneys is most commonly linked to drugs. In allografts, it is a rare complication, and it occurs mostly with infections. CASE PRESENTATION: Our case report presents AGIN with simultaneous acute cellular rejections and acute tubular necrosis in a kidney transplant patient 2 weeks after intravenous application of zoledronic acid. A kidney biopsy showed signs of destructive AGIN with acute cellular rejection. After treatment with methylprednisolone pulses and immunosuppressive therapy modification, rebiopsy confirmed complete regression of AGIN with less intense persistent acute cellular rejection and acute tubular necrosis. Kidney function improved after glucocorticoid and intravenous immunoglobulin G therapy. CONCLUSION: To our knowledge, this is the first case of AGIN related to bisphosphonate zoledronate in a kidney transplant patient with consequent acute cellular rejection. In using intravenous zoledronate infusion in a kidney transplant recipient, we should be aware that it could potentially induce acute granulomatous tubulointerstitial nephritis and acute rejection.
.

Kidney Transplantation in Slovenia From 1970 to 2015.

This report gives an overview of kidney transplantation in Slovenia, a country with a population of 2.1 million and one transplant center. The establishment of a national transplant organization resulted in the acceptance of Slovenia into Eurotransplant (ET) in 2000. Between 1970 and 2015, 1158 kidney transplantations were performed. From 1970 to 2009, 126 patients were transplanted from living related donors, only two in the ET period. From 1986 to 1999, 239 patients received kidney grafts from deceased donors, while 793 patients were transplanted from deceased donors after joining ET. In ET period, 1- and 5-year patient survival rates were 98.1% and 93.8%, and the concomitant graft survival rates were 94.3% and 87.5%, respectively. During the ET period, the number of deceased donor kidney transplants per year was three times higher than in the 14 years before. Patient and graft survival rates have been very good and entirely comparable to those in large reports.

Six-Minute Walk Test in Renal Failure Patients: Representative Results, Performance Analysis and Perceived Dyspnea Predictors.

OBJECTIVES: Six-minute walk test in dialysis population hasn't been consistently evaluated for the isolated impact of renal failure and other predictive factors. We measured six-minute walk distance in patients representative for low level of comorbidity and searched for potentially modifiable predictive factors of performance and dyspnea. METHODS: This was a cross-sectional study with hemodialysis patients (N = 90) and control subjects (N = 140). MAIN OUTCOME MEASURES: six-minute walk test distance and dyspnea severity using the 10-item Borg scale. RESULTS: Median distance decreased from 600m below the 6th decade to 420m in the 8th decade of age. Dialysis dependence predicted 101.5m shorter distance in the adjusted model that explained 70% of variability in results. Adjusted for significant covariates of age, height and spontaneous gait speed, fat mass (but not lean body mass) and serum total iron binding capacity were significantly associated with distance (95% CI for B coefficients -4.6 to -1.4 m/kg and 0.1 to 5 m/µmol/l, respectively). Serum total iron binding capacity as an explanatory variable was superior to C-reactive protein and albumin. Dialysis dependence, odds ratio (OR) 2.97 (1.11-7.94), spontaneous gait speed, OR 0.08 (0.02-0.41), rate-pressure product, OR 1.15 (1.08-1.23) and hemoglobin, OR 0.95 (0.92-0.98) predicted dyspnea in the adjusted model. CONCLUSIONS: Renal failure without the confounding effect of comorbidity is a significant negative predictor of performance at six-minute walk test and perceived level of dyspnea. Body fat mass and serum total iron binding capacity are the main potentially modifiable predictors of performance, total iron binding capacity being superior to C-reactive protein and albumin. Although hemoglobin is not associated with test performance, it negatively predicts perceived shortness of breath.

Plasmapheresis and immunoadsorption for treatment and prophylaxis of recurrent focal segmental glomerulosclerosis in adult recipients of deceased donor renal grafts.

Recurrent focal segmental glomerulosclerosis has a great impact on kidney graft survival. This retrospective study presents immunoadsorption-plasmapheresis treatment and outcome in our renal graft recipients with significant post-transplant proteinuria (>1 g/day) and focal segmental glomerulosclerosis in native kidneys. Recurrence was defined as occurrence of nephrotic range proteinuria or biopsy-confirmed diagnosis. Successful treatment was defined as sustained reduction of proteinuria to <1 g/day. From 2000 through 2011, 548 adult patients received kidney grafts from deceased donors. In 20 of these patients (3.6%) end-stage renal disease was a consequence of focal segmental glomerulosclerosis. Recurrence was confirmed in five of seven treated patients. Immunoadsorption-plasmapheresis treatment was successful in five patients (70%). Their age at disease diagnosis in native kidneys was 12 to 44 years. Time to end-stage renal disease was 3 to 14 years. Recipient age at transplantation was 21 to 61 years. Onset of significant proteinuria was 2 to 87 days after transplantation. Immunoadsorption or plasmapheresis started 1 to 7 days after recurrence of significant proteinuria. Treatment period was 1 to 103 months and 12 to 206 procedures were performed per patient. Follow-up period after cessation of plasmapheresis was 11 to 58 months. Final urine protein/creatinine ratio was 8.8 to 98.0 mg/mmol and final serum creatinine was 63 to 148 µmol/L. Follow-up after transplantation was 18 to 135 months. One patient was still on treatment. One graft was lost to recurrence. No serious adverse effects occurred during immunoadsorption and plasmapheresis. Immunoadsorption and plasmapheresis appears to be successful in the majority of patients, probably due to their early start.

Treatment of anemia with epoetin in kidney transplant recipients.

The aim of this study was to analyze the prevalence and efficacy of renal anemia treated with epoetin in maintenance kidney transplant recipients in Slovenia. By the end of 2009, 107 out of 537 patients (19.9%) had been treated with epoetin. A cohort of 49 patients (45.8%) were analyzed in detail: 11 patients received epoetin alpha, 18 epoetin beta, 10 darbepoetin alpha, and 10 patients received methoxy polyethylene glycol-epoetin beta. The median epoetin dose was 0.36 µg/kg body weight per week. The median serum laboratory parameters were as follows: hemoglobin 120 g/L, hematocrit 0.36, ferritin 332 ng/mL, transferrin saturation 34%, serum creatinine 145 µmol/L, serum albumin 41 g/L, intact parathyroid hormone 79 ng/L, and C-reactive protein 3 mg/L. We concluded that the prevalence of renal anemia in kidney transplant recipients treated with epoetin was approximately 20%, and laboratory parameters suggested that the treatment of renal anemia in this study cohort was optimal.