High mortality in the first year after kidney graft failure.

BACKGROUND: The aim of our cohort study was to assess survival of the patients after kidney graft failure. METHODS: Patients starting dialysis after graft failure between January 1, 2004 and December 31, 2010 were identified from the Slovenian Renal Replacement Therapy (RRT) Registry and followed to December 31, 2011. The control group consisted of 351 incident dialysis patients, who were kidney transplant candidates. Survival data were not censored for retransplantations. RESULTS: After a median of 7.4 (interquartile range [IQR]) 0.4-13.0) years with a functioning graft and a median of 15.5 (IQR 7.8-20.7) years on RRT 82 patients started dialysis. Their mean (± standard deviation [SD]) age was 50.4 ± 12.7 years vs 49.2 ± 13.9 years for the incidental transplantation candidates (P = .49). There were sixty-one percent men (vs 64%; P = .67), and all subjects were on hemodialysis treatments. By Dec 31, 2011, 19 (23%) patients had undergone retransplantation and 27 (33%) died after a median of 1.6 (IQR 0.2-5.4) months on dialysis. The causes of death were infection (n = 15), cardio-disease-vascular (n = 6), malignancy (n = 4), or cerebrovascular (n = 2). Deceased patients were significantly older: 60.0 ± 7.9 vs 45.7 ± 12.0 years (P < .001) and more often men: (78% vs 53% P = .05). The unadjusted overall 1- and 3-year survivals rates after graft failure of 70% and 68% were significantly lower than those in the control candidate group of (98% and 93%, respectively (log-rank; P < .001). This difference remained significant upon multivariate analysis (hazard ratio [HR], 12.0; P < .001). The subgroup of 53 patients who started dialysis after chronic graft failure showed unadjusted 1- and 3-year survival rates of 82% and 80%, respectively which were still worse than the control group (P = .001), a difference that remained significant upon multivariate analysis (HR, 1.75; P < .001). CONCLUSION: After kidney graft failure patients experienced increased mortality in the first year after restarting dialysis. However, subjects who survived the first year showed good survival thereafter.

Plasma exchange and intravenous immunoglobulin in the treatment of antibody-mediated rejection after kidney transplantation: a single-center historic cohort study.

BACKGROUND: Antibody-mediated rejection (AMR) of a kidney graft has been increasingly recognized as an important cause of graft failure. Our historic cohort study sought to analyze its treatment and outcomes at our center. METHODS: All patients with AMR between 2005 and 2011 were treated with plasma exchange (PE), intravenous low-dose cytomegalovirus (CMV) hyperimmune globulin, and adjustment of basal immunosuppression. We analyzed data regarding baseline characteristics, rejection treatment with focus on PE, complications, and 1-year outcomes. RESULTS: Twenty-three AMRs occurred in 23 patients (10 male, 13 female) of mean age 41 ± 16 years, all recipients of deceased-donor kidneys with a median of 3 HLA mismatches. The subjects had a median peak panel-reactive antibodies (PRA) of 7% (interquartile range [IQR] 1%-10%). Basal serum creatinine was 174 ± 84 µmol/L estimated glomerular filtration rate (eGFR) (eGFR 42 ± 22 mL/min/1.73 m(2)), while 3 patients were dialysis- dependent. Median period between transplantation and rejection was 38 months (IQR 1.5-88.5). Concomitant T-cell-mediated rejection was treated in 78% of cases. Median number of PE procedures per patient was 10 (range, 5-17). Treatment was estimated to be successful in 83%. Donor-specific antibodies documented in 12 patients (52%) disappeared or showed reduced titers in 7/10 patients with repeated measurements. An infection was present during treatment in 7 (30%) patients. Among 237 PE, there was 1 (0.4%) mild allergic reaction to fresh frozen plasma and significant metabolic alkalosis occurred after 7 (3%) procedures. One year after rejection the mean serum creatinine level was 144 ± 52 µmol/L and Kaplan-Meier estimated graft and patient survival rates were 62% and 95%, respectively. CONCLUSIONS: Intensive treatment with PE, intravenous immunoglobulin, and adjustment of basal immunosuppression were safe and effective to reverse AMR with improved graft function in the majority of patients. However, AMR was associated with markedly decreased 1-year graft survival and the optimal treatment remains uncertain.

Functional status of hemodialysis arteriovenous fistula in kidney transplant recipients as a predictor of allograft function and survival.

There is no accepted policy for preserving or ligating arteriovenous fistula (AVF) after successful kidney transplantation. The aim of this study was to compare kidney graft function and survival between patients with a functional AVF at 1 year after-transplantation with those having a nonfunctional AVF. This historical cohort study included 311 kidney transplant recipients between January 2000 and December 2008 with a functional AVF at the time of transplantation. Patients were divided into 2 groups according to functional status of AVF at 1 year after transplantation. Graft function was assessed at 1 year by serum creatinine and estimated glomerular filtration rate (eGFR) using the 4-variable Modification of Diet in Renal Disease formula. Kaplan-Meier and Cox proportional hazards analyses were used to assess the relationship between the functional status of the AVF and graft survival. The 311 recipients had a mean age of 47 ± 11 years (range, 14 to 70) with 188 (60.5%) males. Patients with functional AVF at 1 year (n = 239) showed higher serum creatinine and lower eGFR values than those with nonfunctional AVF (n = 72): namely 110 ± 38 µmol/L and 69 ± 21 mL/min/1.73 m(2) versus 99 ± 30 µmol/L and 74 ± 19 mL/min/1.73 m(2), respectively (P < .05). Persistence of a functional AVF at 1 year after transplantation was associated with a greater incidence of eGFR <60 mL/min/1.73 m(2) compared with nonfunctional AVF: 36.8% versus 23.6% (odds ratio, 1.885; 95% confidence interval [CI], 1.031-3.450; P = .038). The 5-year allograft survival rates were 60% among patients with a functional AVF versus 75% among those with a nonfunctional AVF (P = .045). The adjusted analyses revealed the persistence of a functional AVF to be associated with an increased risk for future allograft loss (hazard ratio, 1.336; 95% CI, 1.018-1.755; P = .037). In conclusion, the persistence of a functional AVF was associated with a lower eGFR at 1 year after-transplantation and an increased risk for future allograft loss.

Early kidney graft size and Doppler parameters are associated with kidney graft function 1 year after transplantation.

BACKGROUND: The aim of this study was to assess the association of various ultrasonography (US) and Doppler parameters of kidney graft as measured at 1 month posttransplant with 1-year graft function. MATERIALS AND METHODS: The study cohort included 125 adult recipients of deceased donor kidney transplantations between January 2006 and February 2009. All patients underwent an US-Doppler examination performed by a trained nephrologist at 1 month posttransplant using an Acuson-Siemens Sequoia 512. Graft length and intrarenal Doppler indices were measured at the midsegmental artery level. Relative graft size was calculated by dividing graft length with body mass index. Graft function was assessed at 1 year by estimated glomerular filtration rate (eGFR) using the 4-variable Modification of Diet in Real Disease study equation. Linear and logistic regression analyses were used to assess the relationship between US-Doppler parameters and eGFR. RESULTS: Univariate linear regression showed a significant correlation between eGFR at 1 year and graft length at 1 month (P = .009), relative graft length <0.50 cm per kg/m(2) (P = .004), resistance index >0.75 (P = .031), and end-diastolic velocity <9 cm/sec (P = .006). Logistic regression analyses showed that eGFR <60 mL/min/1.73 m(2) at 1 year was significantly associated with graft length <12 cm at 1 month (odds ratio [OR], 2.4; 95% confidence interval [CI], 1.16-4.92; P = .017), relative graft length <0.5 cm per kg/m(2) (OR, 2.54; 95% CI, 1.20-5.35; P = .014), resistance index >0.75 (OR, 2.86; 95% CI, 1.30-6.29; P = .009), and end-diastolic velocity <9 cm/sec (OR, 2.37; 95% CI, 1.01-5.56; P = .047). CONCLUSION: In this retrospective analysis, kidney transplant recipients with greater graft length at 1 month, specifically when standardized to body size, showed better graft function at 1 year posttransplantation. Higher intrarenal diastolic blood flow and lower resistance index at 1 month were also predictive of better graft function at 1 year.

Regional citrate anticoagulation for hemodialysis: calcium-free vs. calcium containing dialysate - a randomized trial.

BACKGROUND: The majority of citrate protocols for hemodialysis (HD) use calcium (Ca)-free dialysate, a limited number use dialysate with Ca, aiming to simplify the procedure. This randomized clinical study sought to compare the anticoagulant effect of citrate using Ca-free dialysate and dialysate with Ca 1.25 mmol/L. METHODS: Fifty HD procedures (in 5 chronic HD patients treated by chronic citrate anticoagulation) were randomly assigned to Ca-free dialysate (25 procedures) or Ca-1.25 dialysate (25 procedures), both with Mg 0.5 mmol/L, Na 138 mmol/L, and bicarbonate 28 mmol/L. Ca-free HD: 15% Na3 citrate 80 ml/hour was infused into the arterial line, and 1 M CaCl2, 14 ml/hour into the venous line. Ca-1.25 group: 15% Na3 citrate 100 ml/hour, 1 M CaCl2 2-4 ml/hour. Polyflux H dialyzers were used. Antithrombotic effect was assessed visually after HD at 3 points: dialyzer, arterial, and venous bubble traps, using a score of 5 (no clotting) to 1 (total clotting). RESULTS: Ca-free group: arterial bubble trap score 4.7 +/- 0.5, dialyzer 4.5 +/- 0.6, venous bubble trap 4.8 +/- 0.6. Ionized calcium (iCa) at dialyzer inlet 0.34 +/- 0.17, outlet 0.21 +/- 0.06 mmol/L. All HDs were completed successfully. Ca-1.25 group: arterial bubble trap score 4.7 +/- 0.5 (NS), dialyzer 2.6 +/- 1.04 (p<0.01), venous bubble trap 2.4 +/- 0.9 (p<0.01). Volume of clot in venous bubble trap was 1.9 +/- 1.8 mL (range 0.5-6 mL). iCa at dialyzer inlet 0.24 +/- 0.05 mmol/L (p<0.05), outlet 0.63 +/- 0.11 mmol/L (p<0.01). Four of 25 HD procedures (16%) were prematurely terminated due to threatening dialyzer clotting, in 6/25 HD procedures (24%), the venous line was changed (p<0.01). CONCLUSION: Citrate anticoagulation with Ca-1.25 dialysate resulted in significantly worse anticoagulation of dialyzer and venous bubble trap compared with Ca-free dialysate, despite higher citrate dose.

Citrate anticoagulation for postdilutional online hemodiafiltration with calcium-containing dialysate and infusate: significant clotting in the venous bubble trap.

BACKGROUND: The aim of this prospective clinical study was to assess safety and antithrombotic efficacy of a regional citrate anticoagulation protocol for postdilutional online hemodiafiltration (HDF) with calcium-containing dialysate and infusate. METHODS: Nineteen postdilutional online HDF procedures with citrate anticoagulation were performed in 9 end-stage renal disease patients. Calcium-containing (1.25 mmol/L dialysate/infusate, 15% (0.51 mol/L) trisodium citrate and 1 mol/L calcium chloride (when necessary) were used; the blood flow was 300 ml/min. Antithrombotic effect was assessed visually after HDF at 3 points: the dialyzer, arterial bubble trap, and venous bubble trap, using a score of 5 (excellent anticoagulation) to 1 (total clotting). The study was terminated prematurely due to frequent clotting in the venous bubble trap. RESULTS: The mean duration of HDF was 4.3 +/- 0.9 hours; infusion volume was 13 +/- 2 L. Almost half of the HDF procedures (9/19, 47%) were completed with some difficulty: in 1 case (1/19, 5%) there was total system clotting; in the other 8 cases, system clotting was threatening and dialysis was terminated prematurely, but in only 4/19 cases (21%) prior to 4-hour duration. The main point of clot formation was the venous bubble trap (score 2.6 +/- 1.0), while anticoagulation was very good at the dialyzer (4.0 +/- 1.2) and excellent at the arterial bubble trap (4.8 +/- 0.9). No side effects were noted, and metabolic consequences were moderate. CONCLUSIONS: Regional citrate anticoagulation using calcium-containing dialysate/infusate during postdilutional online hemodiafiltration results in a high incidence of venous bubble trap clotting.

Effective immunoprophylaxis with basiliximab plus triple therapy in renal transplantation: five-year single-center experience.

We studied prospectively the efficacy and safety of basiliximab combined with triple immunosuppression in adult recipients of > or = 1 HLA-mismatched deceased donor renal grafts. All studied patients received equal immunosuppressive drugs: 20 mg infusion of basiliximab on day 0 and on day 4, cyclosporine microemulsion (Neoral), mycophenolate mofetil, and methylprednisolone. An analysis of 1-year data assessed the incidence of acute rejection episodes, safety of this therapy, renal graft function, and patient and graft survivals. One hundred seventy-two patients were studied. The HLA-antigen mismatches were 2.9 +/- 0.9 (mean +/- SD), and the cold ischemia time was 22.0 +/- 7.5 hours. Fifty-three (31.5%) patients experienced delayed graft function. At 12 months, 5 (3.0%) patients experienced acute rejection. Six renal grafts were lost, but not from rejection. Two patients died. Sixty-six infections required treatment in the hospital. One carcinoma of cervix (in situ) and two basal cell carcinomas of skin were detected. Hypersensitivity reactions and cytokine-release syndrome were not observed. At 12 months, serum creatinine was significantly higher (119 +/- 46 micromol/L; P < .001) in patients with delayed graft function than in patients with immediate graft function (99 +/- 26 micromol/L). Patient and graft survivals were 98.8% and 97.1%, respectively. Basiliximab combined with this triple therapy was an efficient and safe immunosuppression strategy, demonstrated with very low incidence of acute rejections, an acceptable adverse event profile, excellent graft function, and high short-term survival rates in adult recipients of deceased donor renal transplant.

Follow-up of kidney graft recipients with cyclosporine-associated hemolytic-uremic syndrome and thrombotic microangiopathy.

The study was based on 462 patients who underwent kidney transplantation from 1986 through 2004. Cyclosporine (CsA)-related thrombotic microangiopathy (TMA) was observed in 15 (3.3%) patients. The donor ages ranged from 9 to 51 years and cold ischemia times from 12 to 31 hours. Hemolytic-uremic syndrome (HUS) developed 2 weeks after transplantation in 14 patients and later in 1 subject. Histopathologic examination demonstrated glomerular-type TMA in 3 patients, a mixed type (glomerular and vascular) in 11 patients, and a nonspecific mesangial widening with tubulointerstitial lesions in 1 patient. Follow-up biopsies revealed resolution of TMA in 4 patients and chronic vascular TMA in 1 patient. Six patients with mixed-type TMA needed transient hemodialysis. No patient with the glomerular-type TMA needed dialysis (P = .103), and 14 of 15 had good resolution of graft function after CsA dose reduction or temporary discontinuation or continuation of optimal dose. Only 1 graft with mixed-type TMA was lost due to irreversible HUS. The mean glomerular filtration rate (GFR), predicted by the Nankivell equation, was 76 +/- 13 mL/min and 80 +/- 27 mL/min at 1 month after discharge for glomerular- and mixed-type TMA, respectively (P > .05). GFRs 1 year after HUS were 82 +/- 12 and 87 +/- 21 mL/min for the glomerular and the mixed types, respectively (P > .05). We concluded that the mixed-type TMA was associated with a more severe early clinical course than the glomerular-type TMA. The 1-year prognosis was good in the majority of patients, with no significant differences between those with the glomerular- and mixed-type TMA.

High-grade renal transplant artery stenosis after suboptimal angioplasty: favourable long-term outcome.

The purpose of our report is to present the long-term outcomes of three renal transplant recipients with high-grade stenosis and suboptimal percutaneous angioplasty (PTA) because of technical difficulties. Two men and one woman of age 67, 53, and 54 years, who maintained functional cadaveric graft for 17, 9, and 13 years, and had diagnosed significant renal transplant artery stenosis at 2, 1, and 2 years after renal transplantation, respectively, were studied. Stenoses were diagnosed angiographically in the first patient and by Doppler in other two patients, then confirmed by angiography. All three patients had difficult-to-treat hypertension with deterioration of graft function in the presence of or after introducing ACE-inhibitor therapy. PTA was performed in all patients with suboptimal or unsuccessful results as assessed by angiography or control Doppler examination--the residual stenosis was significant and practically unchanged. Surgery was not performed because of high risk, so patients were further treated conservatively. Hypertension was treated avoiding ACE inhibitors. Twelve, 7, and 7 years after angioplasty the serum creatinine is stable in all patients, even decreased compared to pre-PTA and early post-PTA levels, namely, 134, 102, and 75 micromol/L, respectively. Control Doppler examinations revealed a residual stenotic jet in all patients, with slightly decreased peak systolic velocity over time, indicating a slightly decreased grade of stenosis. These observations suggest that renal transplant artery stenosis, even of high grade, can be stable, or even regress with time with excellent long-term graft survival. Randomized studies comparing conservative treatment versus revascularization are warranted.

Cyclic voiding urosonography for detecting vesicoureteric reflux in renal transplant recipients.

BACKGROUND: The clinical significance of vesicoureteric reflux (VUR) in renal transplant recipients remains controversial. Voiding urosonography (VUS), a new modality for detecting VUR, can be used in these patients. The sensitivity of X-ray and radionuclide cystography for detecting VUR may be improved with cyclic procedures. The aim of our study was to evaluate whether cyclic VUS is superior to the single-cycle procedure. METHODS: Cyclic VUS was performed in 27 renal transplant recipients. Eight were children or adolescents and the remaining 19 recipients were adults. VUS was performed according to accepted guidelines. After the first micturition, the catheter was left in place and the entire procedure was repeated under the same conditions. RESULTS: Both initial cycle and cyclic VUS detected 17 out of 27 (63%) VURs in the same patients. The sensitivity was not improved by cyclic VUS. However, there were differences between the initial cycle and cyclic VUS (P=0.028) when comparing the number of negative results and the grades of VURs detected. This difference was even more pronounced when analysing only positive results. In the initial cycle, five out of 17 (29%) VURs were grade III, compared with 10 out of 17 (59%) grade III VURs in the same patients using the cyclic procedure (P=0.008). CONCLUSIONS: Cyclic VUS did not improve the detection sensitivity for VUR in our study. However, given that VUR grade may be important for the management of renal transplant recipients, the use of cyclic VUS may provide a useful diagnostic tool for these patients.

Low-flux versus high-flux synthetic dialysis membrane in acute renal failure: prospective randomized study.

The influence of dialyzer membrane on the morbidity and mortality of patients with acute renal failure remains a matter of debate. The aim of the prospective randomized clinical study was to assess the influence of the flux of a synthetic dialyzer membrane on patients' survival rate, restitution of renal function, and duration of hemodialysis treatment of patients with acute renal failure as a part of multiorgan failure. Seventy-two patients treated in intensive care units of the University Medical Center Ljubljana were randomized according to the dialyzer used throughout the duration of hemodialysis treatment. There were 38 patients in the low-flux group (dialyzer F6, low-flux polysuphone, Fresenius, Bad Homburg, Germany) and 34 patients in the high-flux group (dialyzer Filtral 12, sulphonated high-flux polyacrylonitrile, Hospal, Industrie Meyzieu, France). Both groups were balanced in terms of sex, age, APACHE II score, oliguria before dialysis, cause of acute renal failure, inotropic support, mechanical ventilation, and the number of failing organs. The patients' survival rate was 18.7% in the low-flux group and 20.6% in the high-flux group. Ten patients (26.3%) recovered their renal function in the low-flux group and 8 (23.5%) in the high-flux group. Hemodialysis treatment lasted 11.2 days in the low-flux and 10.7 days in the high-flux group. An analysis of subgroups with a lower mortality rate (subgroup of patients without oliguria and subgroup of patients with less than 4 failed organ systems) did not show significant differences between the low-flux and high-flux groups in terms of survival rate, recovery of renal function, and duration of hemodialysis treatment. In conclusion, no significant differences were found in the results of low-flux versus high-flux synthetic membrane dialyzer treatment in patients with acute renal failure as a part of multiorgan failure in terms of survival rate, recovery of renal function, incidence of oliguria during hemodialysis, and duration of hemodialysis treatment. The number of failing organs seems to be the most important single factor determining the survival of patients with acute renal failure as a part of multiorgan failure.