Pentosidine and its deposition in renal tissue in renal transplantation

BACKGROUND: Advanced glycation end products (AGEs) accumulate in lesions of arteriosclerosis, Alzheimer's disease, rheumatoid arthritis, diabetic retinopathy, and diabetic nephropathy. Among AGEs, chemical quantification and immunohistologic methods for pentosidine have been established. Free pentosidine-eliminated by renal excretion- is mainly affected by renal function. In this study, we measured concentrations of plasma free and total pentosidine and immunohistologically investigated kidney graft biopsy specimens in patients after renal transplantation to investigate the renal function, plasma free and total pentosidine, and its relationship with deposition in the renal tissue. PATIENTS AND METHODS: In 28 patients who underwent renal transplantation from 1996 to 2003, we measured the time course of plasma concentrations of free pentosidine, total pentosidine, and serum creatinine starting right after renal transplantation. Thirty-four graft biopsy specimens were immunohistologically investigated using anti-pentosidine antibody. Plasma free and total pentosidine, and serum creatinine were measured at the same time. RESULTS: Plasma free and total pentosidine were positively correlated with serum creatinine. Plasma free pentosidine and serum creatinine reached nadir values on day 34.2 +/- 14.2, when the blood concentrations were 5.1 +/- 1.6 pmol/mL and 1.7 +/- 0.7 mg/dL, respectively. Plasma total pentosidine reached a nadir on day 116.5 +/- 39.7 when the plasma concentration was 4.0 +/- 1.5 pmol/mg. We correlated the time required to reach the nadir of plasma free and total pentosidine concentrations. However, neither the concentration of plasma free nor plasma total pentosidine at nadir correlated with serum creatinine. The intensity of immunostaining with anti-pentosidine antibody in proximal tubular cells was graded as weakly positive, positive, or strongly positive. Significant differences were obtained among plasma free pentosidine values between the weakly positive and strongly positive groups. CONCLUSIONS: Renal transplantation improves renal function and decreases renal excretion of free pentosidine. Accordingly, total pentosidine also decreases. However, the concentrations of plasma free and total pentosidine at nadir varied among individuals; the blood concentrations were not determined by renal function alone. It was suggested that deposition of pentosidine in proximal tubular cells was more severe among patients with higher plasma free pentosidine and serum creatinine values.     

Visceral fat is better related to impaired glucose metabolism than body mass index after kidney transplantation

The role of visceral adipose tissue (VAT) in post‐transplant hyperglycaemia is not known. We evaluated 167 patients without diabetes 8‐10 weeks after kidney transplantation, performing oral glucose tolerance tests and measuring VAT content from dual‐energy X‐ray absorptiometry scans. Median VAT weight in normal glucose tolerance patients was 0.9 kg, impaired fasting glucose patients 1.0 kg, impaired glucose tolerance patients 1.3 kg and patients with post‐transplant diabetes (PTDM) 2.1 kg (P = 0.004, indicating a difference between groups). Percentage VAT of total body fat was associated with fasting (R² = 0.094, P < 0.001) and 2‐h glucose concentration (R² = 0.062, P = 0.001), while BMI was only associated with 2‐h glucose concentration (R² = 0.029, P = 0.028). An association between BMI and 2‐h glucose concentration was lost in adjusted models, as opposed to the associations between VAT as percentage of total body fat and glucose concentrations (R² = 0.132, P < 0.001 and R² = 0.097, P = 0.001, respectively for fasting and 2‐h glucose concentration). In conclusion, VAT is more closely related to impaired glucose metabolism than BMI after kidney transplantation. The association with central obesity should encourage additional studies on lifestyle interventions to prevent PTDM.     

Impact of parathyroidectomy on allograft outcomes in kidney transplantation

We performed retrospective, multi‐center study of the impacts of parathyroidectomy (PTX) after or before kidney transplantation on allograft outcomes. A total of 63 patients who underwent PTX after kidney transplantation were identified. Deterioration in eGFR by more than 25% at 1 month after PTX occurred in 20% of the patients. The baseline eGFR was significantly lower in impairment group than nonimpairment group [adjusted odds ratio (OR) 0.87, 95% confidence interval (CI) 0.77–0.99, P = 0.033]. Low iPTH concentration after PTX was also a significant risk factor for the renal impairment (OR 0.96, CI 0.94–0.99, P = 0.009). A total of 37 patients who underwent PTX before transplantation were identified. Thirty‐six percent of the patients had persistent hyperparathyroidism by 1 year after transplantation. A high iPTH level before PTX was a significant risk factor for persistent post‐transplant hyperparathyroidism (adjusted OR 1.002, CI 1.000–1.005, P = 0.039). Finally, eGFR values during the first 5 years after transplantation were significantly lower in the patients who underwent PTX at less than 1 year after transplantation, than the pretransplant PTX patients (P = 0.032). As PTX after kidney transplantation has a risk of deterioration of allograft function, pretransplant PTX should be considered for patients with severe hyperparathyroidism, who could undergo post‐transplant PTX.     

Does timing of post‐renal transplant diuresis affect graft survival in live‐donor renal transplants?

Study Type – Prognosis (case series)
Level of Evidence 4 What’s known on the subject? and What does the study add? Delayed graft function had an adverse impact upon graft survival in deceased kidney transplantation. The current study provides evidence of a similar effect in an exclusive live donor renal recipient population.

OBJECTIVE

To study the effect of timing of diuresis on short and long term graft survival in live‐donor (LD) renal transplants.

METHODS

Between 1976 and 2005, 1747 consecutive LD renal transplants were performed in a single institution. Patients were classified according to timing of diuresis after vascular de‐clamping; group 1 included patients with diuresis within 10 min; group 2 started diuresis between 10 and 60 min after de‐clamping; group 3 started diuresis between 1 and 24 h after de‐clamping; and group 4 started diuresis >24 h after de‐clamping. Patients’ data were stored on an electronic database and were reviewed for risk factors and clinical relevance of timing of diuresis.

RESULTS

Groups 1–4 comprised 1598 (91.5%), 87 (5%), 44 (2.5%) and 18 (1%) patients, respectively. By multivariate analysis, vascular thrombosis was the significant risk factor for delayed diuresis. Delayed diuresis was significantly associated with the occurrence of acute tubular necrosis (ATN), and acute and chronic rejection. Graft and patient survival rates were significantly affected by the timing of diuresis. The 1‐year graft survival rates were 93.8, 83.0, 83.6 and 55.6%, and the 5‐year graft survival rates were 77.4, 59.4, 69.4 and 35.7% in groups 1, 2, 3 and 4, respectively (P < 0.001). The 1‐year patient survival rates were 96.5, 84.4, 90.7 and 61.1% and the 5‐year patient survival rates were 87.1, 72.0, 78.1 and 52.4% in groups 1, 2, 3 and 4, respectively (P < 0.001).

CONCLUSION

Delayed diuresis is a rare event after LD renal transplantation, which has an adverse effect on short‐ and long‐term graft and patient survival.     

Visceral fat is strongly associated with post‐transplant diabetes mellitus and glucose metabolism 1 year after kidney transplantation

Body composition after kidney transplantation is linked to glucose metabolism, and impaired glucose metabolism is associated with increased risk of cardiovascular events and death. One year after transplantation, we examined 150 patients for post‐transplant diabetes performing oral glucose tolerance tests and body composition measurements including visceral adipose tissue (VAT) content from dual‐energy X‐ray absorptiometry scans. We found that glucose metabolism was generally improved over the first year post‐transplant, and that the levels of VAT and percentage VAT of total body fat mass (VAT_%totBFM) were lowest in those with normal glucose tolerance and highest in those with post‐transplant diabetes mellitus. In a multivariable linear regression analysis, 87.4% of the variability in fasting glucose concentration was explained by insulin resistance (P<.001, HOMA‐IR index), beta cell function (P<.001, HOMA‐beta), VAT_%totBFM (P=.007), and body mass index (BMI; P=.015; total model P<.001), while insulin resistance (P<.001) and beta cell function (P<.001) explained 31.9% of the variability in 2‐hour glucose concentration in a multivariable model (total model P<.001). VAT was associated with glucose metabolism to a larger degree than BMI. In conclusion, VAT is associated with hyperglycemia one year after kidney transplantation, and insulin resistance and beta cell function estimates are the most robust markers of glucose metabolism.     

BQ-123, a specific endothelin (ETA) receptor antagonist,prevents ischemia-reperfusion injury in kidney transplantation

We studied the effects of the specific endothelin (ET_A) receptor antagonist, BQ-123, on reperfusion injury in a rat model of kidney transplantation. First, Sprague-Dawley rats were divided into three groups: a sham nephrectomy (SNEPH), an autotransplantation (AUTO-Tx), and an allotransplantation (ALLO-Tx) group. In a fourth group, ALLO-Tx+BQ, allografts were flushed with 20 g BQ-123 containing cold Ringer's lactate before transplantation. For the allograft groups, kidneys from white Wistar albino rats were transplanted into allogeneic Sprague Dawley recipients. Grafts were allowed 120 min of reperfusion after 40 min of cold ischemia. ET-1,2 plasma concentrations in the renal venous blood, and kidney tissue prostaglandin (PG) E₂ and leukotriene (LT) B₄ levels were studied. Diene conjugates (DC), hydroxyalkanals (HAA), hydroxyalkenals (HAE) and malondialdehyde (MDA) levels, as the products of lipid peroxidation, and protein carbonyls (PC) and protein sulphydryls (PS), as the parameters of protein oxidation, were also analyzed in the kidney tissue. Plasma ET concentrations increased significantly in the AUTO-Tx and ALLO-Tx groups (P<0.05 and P<0.01, respectively) but this increase was reversed in the ALLO-Tx+BQ group. None of the lipid peroxidation products except DCs (P<0.05) increased in the AUTO-Tx group, whereas they all increased in the ALLO-Tx group (P<0.01). Protein oxidation parameters also changed significantly (P<0.01) in the ALLO-Tx group but did not in the AUTO-Tx group (P<0.05). The differences in PGE₂ and LTB₄ levels were not significant. Histopathologic examination revealed prominent glomerular and tubular injury in the AUTO-Tx and ALLO-Tx groups but less in the ALLO-Tx+BQ group. In the last group, all parameters of lipid peroxidation (P<0.001 for all) and PCs decreased, and PSs were preserved (P<0.001 for both) when compared with the AUTO-Tx and ALLO-Tx groups. We conclude that BQ-123, in addition to inhibiting the binding of ET-1,2 to the ET_A receptor, may also inhibit the release and/or synthesis of ET-1,2 and prevent reperfusion injury in kidney transplantation.     

Advanced glycation end products in children with chronic renal failure and type 1 diabetes

Serum levels of advanced glycation end products (AGEs) are markedly elevated in adults with chronic renal failure (CRF) and diabetes mellitus. Accumulation of AGEs in tissues contributes to the development of long-term complications. Up to now little has been known about the formation of AGEs in childhood. We determined serum levels of the well known AGEs pentosidine and Nɛ-carboxymethyllysine (CML) in children with CRF (n=12), end-stage renal disease (ESRD) (n=9), renal transplantation (n=12), and type 1 diabetes mellitus (n=42) and in healthy children (n=20). Pentosidine was measured by high-performance liquid chromatography (HPLC), CML by a competitive enzyme-linked immunosorbent assay (ELISA) system. Serum levels of pentosidine and CML were significantly higher in the children with CRF and ESRD than in controls (P<0.001), but nearly within the normal range after transplantation. Both AGEs showed a significant negative correlation with creatinine clearance (P<0.001). During a single session of low-flux hemodialysis, total pentosidine and CML levels did not change. Free pentosidine, however, was reduced by 78% (P=0.04). Diabe-tic children showed significantly elevated pentosidine levels (P<0.001) despite normal renal function. We conclude that, similar to adults, increased formation and accumulation of AGEs also exist in children with CRF and type 1 diabetes mellitus. At present the best prevention of AGE-related complications is an early renal transplantation in children with ESRD, as well as a careful metabolic monitoring of diabetics. Received: 25 July 2001 / Revised: 14 November 2001 / Accepted: 18 November 2001     

Influence of hemodialysis membrane type on pentosidine plasma level, a marker of "carbonyl stress".

Influence of hemodialysis membrane type on pentosidine plasma level, a marker of "carbonyl stress." BACKGROUND: The accumulation of advanced glycation end products (AGEs) in uremia has been ascribed to the retention of carbonyl precursors of AGEs. Pentosidine plasma level has been identified as a surrogate marker of carbonyl precursors ("carbonyl stress"). The influence of hemodialysis (HD) membrane type and residual diuresis on carbonyl stress has not been studied. METHODS: We measured protein-linked and free plasma pentosidine (a surrogate marker of carbonyl stress) by high-performance liquid chromatography in patients on HD with low-flux cellulose (N = 29), high-flux polysulfone (PS; N = 57), polymethylmethacrylate (PMMA) (N = 25), and AN69 (N = 15). RESULTS: Both protein-linked and free pentosidine were similar on low-flux cellulose, high-flux PMMA, and AN69, but were lower (P < 0.01) on high-flux PS. Pentosidine levels were virtually identical on Fresenius and Asahi PS in Japanese and Belgian patients. By multivariate analysis, only the type of HD membrane and residual diuresis proved to be independent determinants (P < 0.001) of pentosidine levels. During a single HD session, the clearance of free pentosidine was similar with all membranes. In three patients who were switched from AN69 to PS, the protein-linked pentosidine level dropped to the control level after resumption of the AN69 membrane. CONCLUSIONS: Both HD membrane type and residual diuresis are independent determinants of pentosidine plasma level, which is a marker of carbonyl stress.     

Relationship of transforming growth factor-beta(1) with tumour necrosis factor-alpha and endothelial activation in patients with stable renal transplantation

Aim: To evaluate whether or not transforming growth factor‐beta₁ is related to inflammation markers and to intercellular and vascular cell adhesion molecules in patients with stable renal transplantation. Methods: Serum concentrations of transforming growth factor‐beta₁, tumour necrosis factor‐alpha, C‐reactive protein and adhesion molecules were analysed in 33 renal transplanted patients, 33 patients with chronic renal insufficiency (matched to the transplanted group for level of renal function), and 33 hypertensives with normal renal function. anova , Student's t‐test and simple regression analysis were used to analyse the data. Results: Transplanted patients showed higher values than hypertensives of transforming growth factor‐beta₁, tumour necrosis factor‐alpha, C‐reactive protein and adhesion molecules (P < 0.0001 for all). Renal insufficiency group exhibited higher concentrations of transforming growth factor‐beta₁, tumour necrosis factor‐alpha, C‐reactive protein and adhesion molecules than hypertensives (P < 0.0001 for all). Transplanted and renal insufficiency patients had similar blood pressure and renal function levels, and transforming growth factor‐beta₁, tumour necrosis factor‐alpha, C‐reactive protein and adhesion molecules were not significantly different. In transplanted and in renal insufficiency groups transforming growth factor‐beta₁, adhesion molecules and tumour necrosis factor‐alpha correlated significantly each other and with glomerular filtration rate (P < 0.001 for all). Conclusion: In long‐term renal transplantation inflammation and endothelial activation biomarkers, the pro‐fibrotic cytokine transforming growth factor‐beta₁ and kidney function are interrelated. Because of the relevant role that inflammation, organ fibrosis and graft dysfunction may play against renal and cardiovascular survival of graft recipients, a better comprehension of the interactions between these variables is needed.     

Autosomal dominant polycystic kidney disease: risk factor for nonmelanoma skin cancer following kidney transplantation

Nonmelanoma skin cancers (NMSC) are the most common malignant tumors following solid organ transplantation. Risk factors for NMSC mainly include immunosuppression, age, sun exposure and patient phototype. Recent findings have suggested that autosomal dominant polycystic kidney disease (ADPKD) may increase the risk of developing NMSC. We performed a monocenter retrospective study including all kidney recipients between 1985 and 2006 (n = 1019). We studied the incidence of NMSC, solid cancers and post‐transplantation lymphoproliferative disease (PTLD), and analyzed the following parameters: age, gender, phototype, time on dialysis, graft rank, immunosuppressive regimen, history of cancer and kidney disease (ADPKD versus others). Median follow‐up was 5.5 years (range: 0.02–20.6; 79 838 patient‐years). The cumulated incidence of NMSC 10 years after transplantation was 12.7% (9.3% for solid cancers and 3.5% for PTLD). Autosomal dominant polycystic kidney disease and age were risk factors for NMSC (HR 2.63; P < 0.0001 and HR 2.21; P < 0.001, respectively) using univariate analysis. The association between ADPKD and NMSC remained significant after adjustments for age, gender and phototype using multivariate analysis (HR 1.71; P = 0.0145) and for immunosuppressive regimens (P < 0.0001). Autosomal dominant polycystic kidney disease was not a risk factor for the occurrence of solid cancers after transplantation (HR 0.96; P = 0.89). Our findings suggest that ADPKD is an independent risk factor for developing NMSC after kidney transplantation.     

Pamidronate in the prevention of bone loss after liver transplantation: a randomized controlled trial

Rapid bone loss and high rates of fractures occur following liver transplantation. To analyze the effect of intravenous pamidronate on bone loss after liver transplantation. A randomized, double‐blind, placebo‐controlled study was performed. Seventy‐nine patients were randomized to two groups of treatment: the pamidronate group (n = 38) was treated with 90 mg/IV of pamidronate within the first 2 weeks and at 3 months after transplantation; the placebo group (n = 41) received glucose infusions at the same time points. All patients received calcium and vitamin D. Bone mineral density (BMD) at the lumbar spine (L₂–L₄) and proximal femur using dual energy X‐ray absorptiometry and also spinal X‐rays were performed before, and at 6 and 12 months after liver transplantation. Biochemical and hormonal determinations were performed previous to transplantation, at 24 h before and after treatment, as well as at 6 and 12 months after liver transplantation. At 12 months after transplantation, there were significant differences in lumbar BMD changes (6 months: pamidronate 1.6% vs. placebo 0.8%, P = NS; 12 months: pamidronate 2.9% vs. placebo 1%, P < 0.05). Femoral neck BMD decreased in the pamidronate‐ and placebo groups during the first 6 months (6 months: pamidronate ?3.1% vs. placebo ?2.9%, P = NS; 12 months: pamidronate ?3.2% vs. placebo ?3.1%, P = NS). BMD at the trochanter remained stable in the pamidronate group, whilst a reduction was observed in the placebo group at 6 months (6 months: pamidronate ?0.7% vs. placebo ?3.7%, P < 0.05; 12 months: pamidronate ?0.5% vs. placebo ?1.2%, P = NS). Moreover, no significant differences in the incidence of fractures, serum parathyroid hormone and serum 25‐hydroxyvitamin D values between both groups were found. Pamidronate did not increase the risk of serious adverse events. The results of this study show that 90 mg of intravenous pamidronate within the first 2 weeks and at 3 months following liver transplantation preserve lumbar bone mass during the first year, without significant adverse events. However, pamidronate does not reduce bone loss at the femoral neck and furthermore it does not reduce skeletal fractures.     

The effects of reactive hyperemia on stimulation of endothelium-derived nitric oxide in on-pump and off-pump coronary artery bypass surgeries

The purpose of this study is to compare the effects of cardiopulmonary bypass (CPB) on the endothelium‐derived nitric oxide (NO) levels in on‐pump and off‐pump coronary artery bypass surgeries. Forty consecutive patients were divided randomly into two groups depending on use of CPB in coronary artery bypass graft surgery (group 1: n = 20, off‐pump, and group 2: n = 20, on‐pump). The plasma endothelium‐derived NO levels were determined at baseline and after reactive hyperemia before and after surgery. Reactive hyperemia was induced by inflating a blood pressure cuff placed on the upper forearm, for 5 min at 250 mm Hg followed by a rapid deflation. Blood was collected at 1 min after cuff deflation from the radial artery on the same side. Preoperative use of all medications was recorded. The baseline plasma NO levels before operation were 17.10 ± 7.58 in group 1 and 15.49 ± 5.26 nmol/L in group 2. Before operation after reactive hyperemia, the plasma NO levels were 26.97 ± 11.49 in group 1 and 26.57 ± 12.87 nmol/L in group 2. Two hours after surgery, the plasma NO levels at baseline and after reactive hyperemia were not significantly different from each other (group 1: 18.03 ± 6.37 and group 2: 19.89 ± 9.83 nmol/L; group 1: 27.89 ± 18.36 and group 2: 39.13 ± 23.60 nmol/L, respectively; P > 0.05). A positive correlation was shown between preoperative nitroglycerine use and the postoperative plasma NO levels after reactive hyperemia (r = 0.51, P = 0.001). Linear regression analysis was performed (F = 4.10, R = 0.56, R² = 0.32, P = 0.008) and the only independent parameter that had an effect on postoperative plasma NO levels after reactive hyperemia was found to be preoperative nitroglycerine use (t = 3.68, P = 0.001). Coronary artery bypass surgery with CPB does not have significant effect on plasma endothelial derived NO levels. The postoperative plasma NO levels after reactive hyperemia significantly correlated with preoperative nitroglycerine use.     

Acute and long-term changes in plasma levels of atrial natriuretic factor in patients with renal replacement therapy

In 14 patients on hemodialysis who received kidney grafts from living related donors, plasma levels of immunoreactive atrial natriuretic factor (Ir-ANF) were determined in a sequence covering the last hemodialysis treatment, the day of transplantation, and a follow-up period of 6–12 months. The geometric mean value before dialysis was 196 pg/ml, the range 32–634. Weight loss during dialysis was 1.5±1.1 kg (mean±SD), but only a nonsignificant reduction in Ir-ANF levels occurred. On the day of transplantation, plasma Ir-ANF levels increased from 143 pg/ml before to 391 post-transplantation (P=0.02, n=12), probably in response to deliberate volume expansion. Post-transplant Ir-ANF levels correlated significantly to diuresis during the first 24 h, which ranged from 3.7 to 17.81 (mean 6.6; r=0.65, P=0.02). On day 2, mean 24 h diuresis decreased to 3.3±1.41. Most patients had reached their true dry weight by day 5, but Ir-ANF levels remained high, the geometric mean being 180 pg/ml. During further follow-up and preserved graft function (GFR range 34–88 ml/min per 1.73 m² body surface area), Ir-ANF levels declined to a geometric mean of 63 pg/ml by 2–6 months and to 36 at 12 months post-transplant. We conclude that plasma Ir-ANF levels are chronically elevated in patients with chronic renal failure but may be further stimulated by acute overhydration. Transplanted kidneys initially respond to the increased levels but adapt within a day. Even with good graft function, normalization of plasma Ir-ANF requires several weeks or months.     

Pre-transplant pharmacokinetic profiling and tacrolimus requirements post-transplant

Aim: To determine the proportion of patients achieving tacrolimus whole‐blood concentrations of ≥10 ng/mL within 3 days of kidney transplantation, after randomization either to standard dosing (control group) or post‐transplantation dosing guided by a 2‐hour (C₂) level following a preoperative tacrolimus dose (T2 group). Methods: The first postoperative tacrolimus dose was given either according to standard care (control group) or 0.15 mg/kg b.d. if the pre‐transplant C₂ level was ≤20 ng/mL, 0.1 mg/kg b.d. if the C₂ level was 21–59 ng/mL or 0.05 mg/kg b.d. if the C₂ level was ≥60 ng/mL (T2 group). Subsequent dosing in both groups was based upon tacrolimus trough level monitoring. Participants received concomitant mycophenolate mofetil and steroids. Results: Ninety patients were recruited, of which 84 were included in the analysis (control group n = 43; T2 group n = 41). There was no difference in the proportion of subjects achieving tacrolimus trough levels ≥10 ng/mL (82.9% Control vs 93.0% T2; P = 0.19) or between 10 and 15 ng/mL (41.5% Control vs 41.9% T2; P = 0.97) at day 3 post transplant. The T2 group achieved tacrolimus trough levels of ≥10 ng/mL significantly faster than the control group (100% achievement in 14 days (Control) versus 4 days (T2); P = 0.01). Conclusion: Performing a pre‐transplant tacrolimus C₂ does not significantly increase the high proportion of subjects achieving 10 ng/mL tacrolimus concentrations by day 3 using routine protocols. However, compared with standard care, performing a pre‐transplant tacrolimus C₂ does lead to patients achieving a whole‐blood concentration of ≥10 ng/mL sooner.     

Pre‐existing donor‐specific antibodies are detrimental to kidney allograft only when persistent after transplantation

Donor‐specific antibodies (DSA) increase the risk of allograft rejection and graft failure. They may be present before transplant or develop de novo after transplantation. Here, we studied the evolution of preformed DSA and their impact on graft outcome in kidney transplant recipients. Using the Luminex Single Antigen assay, we analyzed the sera on the day of transplantation of 239 patients who received a kidney transplant. Thirty‐seven patients (15.5%) had pre‐existing DSA detected the day of transplantation. After 5 years, the pre‐existing DSA disappeared in 22 patients whereas they persisted in 12. Variables associated with DSA persistence were age <50 years (P = 0.009), a history of previous transplantation (P = 0.039), the presence of class II DSA (P = 0.009), an MFI of preformed DSA >3500 (P < 0.001), and the presence of two or more DSA (P < 0.001). DSA persistence was associated with a higher risk of graft loss and antibody‐mediated rejection. Previously undetected preformed DSA are deleterious to graft survival only when they persist after transplantation.     

Prognostic value of intraoperative renal tissue oxygenation measurement on early renal transplant function

Ischemia time is a prognostic factor in renal transplantation for postoperative graft function and survival. Kidney transplants from living donors have a higher survival rate than deceased donor kidneys probably because of shorter ischemia time. We hypothesized that measurement of intraoperative kidney oxygenation (μHbO₂) and microvascular perfusion predicts postoperative graft function. We measured microvascular hemoglobin oxygen saturation by reflectance spectrophotometry and microcirculatory kidney perfusion by laser Doppler flowmetry 5 and 30 min after kidney reperfusion on the organ surface in 53 renal transplant patients including 19 grafts from living donors. These values were related to systemic hemodynamics, cold ischemia time (cit), early postoperative graft function and length of hospital stay. μHbO₂ improved 30 min after reperfusion compared to 5 min (from 67% to 71%, P < 0.05). μHbO₂ correlated with mean arterial blood pressure and central venous pH (P < 0.01). Most importantly, μHbO₂ was significantly higher in kidneys from living compared with deceased donors (74% vs. 63%) and in kidneys without vs. with biopsy‐proven postoperative rejection (71% vs. 45%, P < 0.001). Finally, μHbO₂ correlated positively with cit and postoperative creatinine clearance and negatively with postoperative plasma creatinine, need for hemodialysis and length of hospital stay. Our results suggest higher oxygen extraction and thus oxygen demand of the grafts shortly after reperfusion. The intraoperative measurement of tissue oxygenation in kidney transplants is predictive of early postoperative graft function. Future studies should evaluate the potential effect of intraoperative therapeutic maneuvers to improve organ tissue oxygenation in renal transplantation.     

Normothermic ex vivo kidney perfusion for graft quality assessment prior to transplantation

Normothermic ex vivo kidney perfusion (NEVKP) represents a novel approach for graft preservation and functional improvement in kidney transplantation. We investigated whether NEVKP also allows graft quality assessment before transplantation. Kidneys from 30‐kg pigs were recovered in a model of heart‐beating donation (group A) after 30 minutes (group B) or 60 minutes (group C) (n = 5/group) of warm ischemia. After 8 hours of NEVKP, contralateral kidneys were resected, grafts were autotransplanted, and the pigs were followed for 3 days. After transplantation, renal function measured based on peak serum creatinine differed significantly among groups (P < .05). Throughout NEVKP, intrarenal resistance was lowest in group A and highest in group C (P < .05). intrarenal resistance at the initiation of NEVKP correlated with postoperative renal function (P < .001 at NEVKP hour 1). Markers of acid‐base homeostasis (pH, HCO₃^–, base excess) differed among groups (P < .05) and correlated with posttransplantation renal function (P < .001 for pH at NEVKP hour 1). Similarly, lactate and aspartate aminotransferase were lowest in noninjured grafts versus donation after circulatory death kidneys (P < .05) and correlated with posttransplantation kidney function (P < .001 for lactate at NEVKP hour 1). In conclusion, assessment of perfusion characteristics and clinically available perfusate biomarkers during NEVKP allows the prediction of posttransplantation graft function. Thus, NEVKP might allow decision‐making regarding whether grafts are suitable for transplantation.     

Living kidney donation does not adversely affect serum calcification propensity and markers of vascular stiffness

Living kidney donors (LKDs) experience a decline in glomerular filtration rate (GFR) after donation. Calcification propensity (T₅₀) can be determined by a blood test predicting all‐cause mortality in patients with chronic kidney disease. We studied the impact of kidney donation on T₅₀ and markers of arterial stiffness. We analyzed T₅₀ prospectively before and 1 year after kidney donation in 21 LKDs along with fetuin‐A, mineral metabolism markers, kidney length, pulse wave velocity (PWV), augmentation index (AI), and renal resistive index (RRI) as markers of arterial stiffness. We studied the impact of kidney donation on these parameters. LKDs were 54 ± 10 years old and had a GFR of 101 ± 18 ml/min/1.73 m² before donation, decreasing to 67 ± 8 ml/min/1.73 m² after donation (P < 0.001). Despite this, T₅₀ improved after donation (290 ± 53 to 312 ± 38 min, P = 0.049). This change was inversely related to plasma phosphate (P = 0.03), which declined after donation (P = 0.002). Fetuin‐A levels increased after donation (P = 0.01). Upon donation, the length of the remaining kidney increased (P < 0.001) while PWV, AI, and RRI remained unchanged. Calcification propensity was not adversely affected by kidney donation. This indicates that T₅₀ is independent from GFR in LKDs and that kidney donation does neither worsen calcification propensity nor markers of vascular stiffness at 1 year.     

Effects of Sugammadex Plus Rocuronium vs Neostigmine Plus Cisatracurium During Renal Transplantation on Graft Function: A Retrospective,Case-Control Study

BackgroundRocuronium can be used in patients with severe renal failure (creatinine clearance <30 mL/min), but the duration of muscle relaxation is longer and results in an increased risk of postoperative residual neuromuscular block. Rocuronium can be antagonized by sugammadex, but the elimination of the complex they make (rocuronium-sugammadex complex) varies according to the renal function. Two case reports/series have reported the use of rocuronium-sugammadex complex during renal transplantation. A recently published retrospective study showed no differences in postoperative creatinine levels in patients receiving kidney transplantation. This retrospective case-control study aims to investigate the effects of rocuronium-sugammadex, used during renal transplantation, on transplanted kidney function.MethodsWe analyzed 113 medical records of patients undergoing kidney transplantation from January 2015 to December 2018. Forty-seven medical records were excluded because they did not report the administration of one of the following drugs during the transplantation: rocuronium, sugammadex, cisatracurium, neostigmine. The demographics of patients and donors were collected along with the following data: blood urea and creatinine, serum and urinary electrolytes, and diuresis. Marginal, single, or double kidney transplantations; Karpinski scores; and histologic evaluations of transplanted kidney were collected.ResultsWe included data from 66 medical reports from January 2015 to December 2018. Blood creatinine levels at 6, 12, and 24 hours were significantly lower in the rocuronium + sugammadex group than in the cisatracurium + neostigmine group (creatinine 6 hours P = .05, creatinine 12 hours P = .038, creatinine 24 hours P = .049). Blood urea levels for 24 hours after transplantation were significantly lower in the rocuronium + sugammadex group than in the cisatracurium + neostigmine group (urea 0 hours P = .025, urea 6 hours P = .011, urea 12 hours P = .03, urea 24 hours P = .011). We found no statistically significant differences in blood sodium, blood potassium, blood calcium, diuresis, urinary sodium, or urinary potassium levels before and after transplantation.ConclusionsIn this retrospective case-control study, the use of rocuronium and sugammadex during renal transplant surgery did not affect relevant kidney recovery outcomes in the first week after transplantation.     

Association of Serum Pentosidine With Arterial Stiffness in Hemodialysis Patients

Pentosidine is an advanced glycation end product (AGE). The present study was undertaken to investigate the association of serum pentosidine with carotid distensibility as a measure of arterial stiffness in hemodialysis patients. One hundred and three patients on maintenance hemodialysis were recruited. The distensibility coefficient of the common carotid artery was evaluated by an ultrasonic phase‐locked echo‐tracking system. Serum pentosidine was measured by competitive enzyme‐linked immunosorbent assay. Serum albumin, lipid profile, calcium, phosphorus, intact parathyroid hormone (iPTH), high‐sensitivity C‐reactive protein (hs‐CRP), and oxidized low‐density lipoprotein (ox‐LDL) levels were also measured. Correlation was determined by linear and multiple stepwise regression analysis. Serum pentosidine level studied in hemodialysis patients was 0.54 ± 0.13 µg/mL. No significant difference in serum pentosidine level was noted between patients with and without diabetes (0.59 ± 0.10 µg/mL vs. 0.53 ± 0.13 µg/mL, P = 0.062) as well as between patients with and without prior cardiovascular disease (CVD) history (0.56 ± 0.14 µg/mL vs. 0.53 ± 0.12 µg/mL, P = 0.206). In multivariate regression analysis, only age (β = 0.363, P < 0.001) and ox‐LDL (β = 0.262, P = 0.004) were identified as independent determinants for serum pentosidine. Serum pentosidine was significantly correlated with carotid distensibility (r = ?0.387, P < 0.001), as well as age, ox‐LDL, and hs‐CRP. After adjustment for age, blood pressure, history of diabetes, prior CVD history, lipid profile, calcium, phosphorus, iPTH, hs‐CRP, and ox‐LDL, serum pentosidine was still negatively correlated with distensibility (β = ?0.175, P = 0.044). Serum pentosidine was independently associated with carotid distensibility in hemodialysis patients. This finding suggested that the accumulation of AGE might be an important pathway in the development of arterial stiffness in end‐stage renal disease.