Contrast Induced Nephropathy and Long-term Renal Decline After Percutaneous Transluminal Angioplasty for Symptomatic Peripheral Arterial Disease.

OBJECTIVE/BACKGROUND: Administration of iodinated contrast media during endovascular procedures for peripheral arterial disease (PAD) may cause contrast induced nephropathy (CIN). The aim of the present study was to establish the incidence of CIN after these procedures and to study its association with long-term loss of kidney function, cardiovascular events, and death. METHODS: Consecutive patients first presenting with symptomatic PAD (Rutherford classification II-VI) who were treated with an endovascular procedure were included in this prospective observational cohort study. CIN was defined as >25% increase of serum creatinine concentration from baseline at 5 days after the intervention. RESULTS: Some 337 patients were included with a mean estimated glomerular filtration rate (eGFR) of 67 mL/minute. Thirteen percent (95% confidence interval [CI] 9-16) of these patients developed CIN after endovascular interventions for PAD. One year after treatment, eGFR was reduced by 12.4 mL/minute (95% CI 8.6-16.2) in patients with CIN compared with 6.2 mL/minute (95% CI 4.9-7.0) in patients without acute kidney injury (p < .01). After correction for potential confounders, CIN was associated with a 7.8 mL/minute (95% CI 4.5-11.0) reduction of eGFR at 1 year after endovascular intervention (p < .01). Furthermore, patients with CIN were at increased risk of long-term cardiovascular events and mortality. CONCLUSION: Exposure to iodinated contrast media during endovascular procedures for symptomatic PAD frequently results in CIN. Patients with CIN are at increased risk of long-term loss of renal function, cardiovascular events, and death.

The relationship of peritubular capillary density with glomerular volume and kidney function in living kidney donors.

BACKGROUND: Peritubular capillary rarefaction plays an important role in the progression of chronic kidney disease. Little is known about the relation between peritubular capillary density, glomerular volume and filtration rate in the healthy kidney. METHODS: In this single-center study, we included 69 living kidney donors who donated between 2005 and 2008 and had representative renal biopsies available. In all donors, glomerular filtration rate was measured using 125I-Iothalamate before donation and at five years after donation. Before donation, the increase in glomerular filtration rate after dopamine stimulation was measured. Glomerular volume and peritubular capillary density were determined in biopsies taken at the time of transplantation. Pearson's correlation coefficient and linear regression were used to assess relations between parameters. RESULTS: Mean donor age was 52 ± 11 years and mean measured glomerular filtration rate was 119 ± 22 mL/min before donation and 82 ± 15 mL/min at five years after donation. While peritubular capillary density (measured by either number of peritubular capillaries/50,000 µm2 or number of peritubular capillaries/tubule) was not associated with measured glomerular filtration rate before or after donation, number of peritubular capillaries/tubule was associated with the increase in measured glomerular filtration rate after dopamine stimulation (St.ß = 0.33, p = 0.004), and correlated positively with glomerular volume (R = 0.24, p = 0.047). Glomerular volume was associated with unstimulated measured glomerular filtration rate before donation (St.ß = 0.31, p = 0.01) and at five years (St.ß = 0.30, p = 0.01) after donation, independent of age. CONCLUSIONS: In summary, peritubular capillary density was not related to unstimulated kidney function before or after kidney donation, in contrast to glomerular volume. However, number of peritubular capillaries/tubule correlated with the increase in glomerular filtration rate after dopamine stimulation in healthy kidneys, and with glomerular volume. These findings suggest that peritubular capillary density and glomerular volume differentially affect kidney function in healthy living kidney donors.

Risk of anastomotic leakage with non-steroidal anti-inflammatory drugs in colorectal surgery.

BACKGROUND: With the implementation of multimodal analgesia regimens in fast-track surgery programmes, non-steroidal anti-inflammatory drugs (NSAIDs) are being prescribed routinely. However, doubts have been raised concerning the safety of NSAIDs in terms of anastomotic healing. METHODS: Data on patients who had undergone primary colorectal anastomosis at two teaching hospitals between January 2008 and December 2010 were analysed retrospectively. Exact use of NSAIDs was recorded. Rates of anastomotic leakage were compared between groups and corrected for known risk factors in both univariable and multivariable analyses. RESULTS: A total of 795 patients were divided into four groups according to NSAID use: no NSAIDs (471 patients), use of non-selective NSAIDs (201), use of selective cyclo-oxygenase (COX) 2 inhibitors (79), and use of both selective and non-selective NSAIDs (44). The overall leak rate was 9.9 per cent (10.0 per cent for right colonic, 8.7 per cent for left colonic and 12.4 per cent for rectal anastomoses). Known risk factors such as smoking and use of steroids were not significantly associated with anastomotic leakage. Stapled anastomosis was identified as an independent predictor of leakage in multivariable analysis (odds ratio (OR) 2.22, 95 per cent confidence interval 1.30 to 3.80; P = 0.003). Patients on NSAIDs had higher anastomotic leakage rates than those not on NSAIDs (13.2 versus 7.6 per cent; OR 1.84, 1.13 to 2.98; P = 0.010). This effect was mainly due to non-selective NSAIDs (14.5 per cent; OR 2.13, 1.24 to 3.65; P = 0.006), not selective COX-2 inhibitors (9 per cent; OR 1.16, 0.49 to 2.75; P = 0.741). The overall mortality rate was 4.2 per cent, with no significant difference between groups (P = 0.438). CONCLUSION: Non-selective NSAIDs may be associated with anastomotic leakage.

Kidney transplantation from donors after cardiac death: uncontrolled versus controlled donation.

Kidney donation after cardiac death has been popularized over the last decade. The majority of these kidneys are from controlled donors. The number of organs for transplantation can be further increased by uncontrolled donors after cardiac death. The outcome of uncontrolled compared to controlled donor kidney transplantation is relatively unknown. We compared the long-term outcome of kidney transplantation from uncontrolled (n = 128) and controlled (n = 208) donor kidneys procured in the Maastricht region from January 1, 1981 until January 1, 2008, and transplanted in the Eurotransplant region. The incidence of primary nonfunction and delayed graft function in both uncontrolled and controlled donor kidneys is relatively high (22% vs. 21%, and 61% vs. 56%, p = 0.43, respectively). Ten-year graft and recipient survival are similar in both groups (50% vs. 46%, p = 0.74 and 61% vs. 60%, p = 0.76, respectively). Estimated glomerular filtration rates 1 year after transplantation are 40 ± 16 versus 42 ± 19 mL/min/1.73 m(2) , p = 0.55, with a yearly decline thereafter of 0.67 ± 3 versus 0.70 ± 7 mL/min/1.73 m(2) /year, p = 0.97. The outcome of kidney transplantation from uncontrolled and controlled donors after cardiac death is equivalent. This justifies the expansion of the donor pool with uncontrolled donors to reduce the still growing waiting list for renal transplantation, and may stimulate the implementation of uncontrolled kidney donation programs.

Renovascular resistance of machine-perfused DCD kidneys is associated with primary nonfunction.

Donation after cardiac death (DCD) has shown to be a valuable extension of the donor pool despite a higher percentage of primary nonfunction (PNF). Limiting the incidence of PNF is of vital importance. Renovascular resistance is believed to predict graft outcome; however the literature is inconsistent. Therefore, we studied whether renovascular resistance is associated with PNF and whether this parameter should be used to discard donor kidneys. All transplanted DCD kidneys preserved by machine perfusion at our center between 1993 and 2007 were analyzed (n = 440). The effects of renovascular resistance on PNF, delayed graft function (DGF), and graft and patient survival were examined using multivariable analyses; predictive quality by calculating the area under the curve (AUC). We showed that renovascular resistance at the start of machine perfusion was significantly and independently associated with PNF (OR 2.040, 95% CI 1.362-3.056; p = 0.001), and DGF (OR 2.345, 95% CI 1.110-4.955; p = 0.025). Predictive quality was moderate (0.609, 95% CI 0.538-0.681). Graft and patient survival were not associated with renovascular resistance. We conclude that renovascular resistance in DCD kidneys is an independent risk factor for PNF; however, the predictive value is relatively low.

Preservation of kidneys from controlled donors after cardiac death.

BACKGROUND: Donation after cardiac death (DCD) expands the pool of donor kidneys, but is associated with warm ischaemic injury. Two methods are used to preserve kidneys from controlled DCD donors and reduce warm ischaemic injury: in situ preservation using a double-balloon triple-lumen catheter (DBTL) inserted via the femoral artery and direct cannulation of the aorta after rapid laparotomy. The aim of this study was to compare these two techniques. METHODS: This was a retrospective cohort study of 165 controlled DCD procedures in two regions in the Netherlands between 2000 and 2006. RESULTS: There were 102 donors in the DBTL group and 63 in the aortic group. In the aortic group the kidney discard rate was lower (4·8 versus 28·2 per cent; P < 0·001), and the warm (22 versus 27 min; P < 0·001) and the cold (19 versus 24 h; P < 0·001) ischaemia times were shorter than in the DBTL group. Risk factors for discard included preservation with the DBTL catheter (odds ratio (OR) 5·19, 95 per cent confidence interval 1·88 to 14·36; P = 0·001) and increasing donor age (1·05, 1·02 to 1·07; P < 0·001). Warm ischaemia time had a significant effect on graft failure (hazard ratio 1·04, 1·01 to 1·07; P = 0·009), and consequently graft survival was higher in the aortic cannulation group (86·2 per cent versus 76·8 per cent in the DBTL group at 1 year; P = 0·027). CONCLUSION: In this retrospective study, direct aortic cannulation appeared to be a better method to preserve controlled DCD kidneys.

Histological assessment of preimplantation biopsies may improve selection of kidneys from old donors after cardiac death.

Kidneys from old donors after cardiac death (DCD) may increase the donor pool but the prognosis of these kidneys is unsatisfactory. To improve these results, we retrospectively evaluated the diagnostic utility of published selection algorithms for old donor kidneys. We studied all DCD kidney transplantations between January 1, 1994 and July 1, 2005 at our institution (n = 199). Selection algorithms were evaluated in the subset of kidney transplantations from donors aged 60 years or older (n = 52). For histological assessment of kidney biopsies, glomerulosclerosis, tubular atrophy, interstitial fibrosis and vascular narrowing were blindly scored. Functional kidney weight was calculated as renal mass multiplied by the fraction of nonsclerosed glomeruli. Graft function and survival of kidneys from DCD aged 60 years or older were inferior to those from younger DCD. Histological scores were associated with kidney function and graft survival of old DCD kidney transplantations. Functional kidney weight was associated with kidney function but not graft survival, while donor glomerular filtration rate (GFR), donor age and machine perfusion characteristics were associated with neither of the clinical outcomes of interest. We conclude that histological assessment of preimplantation biopsies may improve the selection of kidneys from old DCD and may therefore contribute to expansion of the donor pool.

Recipient hemodynamics during non-heart-beating donor kidney transplantation are major predictors of primary nonfunction.

Non-heart-beating donor (NHBD) kidneys may substantially expand the donor pool, but many transplant centers are reluctant to use these kidneys because of the relatively high incidence of primary nonfunction (PNF). In heart-beating donor kidneys, intravascular fluid depletion during transplant surgery is associated with delayed graft function (DGF). Therefore, we studied the effect of the recipients' hemodynamic status on the outcome of 177 NHBD kidney transplantations. Independent statistically significant predictors of PNF were average central venous pressure (CVP) below 6 cmH(2)O (adjusted odds ratio (AOR) 3.1 (95% CI: 1.4-7.1), p=0.007), average systolic blood pressure below 110 mmHg (AOR 2.6 (95% CI: 1.1-5.9), p=0.03) and pre-operative diastolic blood pressure below 80 mmHg (AOR 2.4 (95% CI: 1.0-5.9), p=0.05). Donor characteristics were not independently associated with PNF (p>0.10). In a subgroup analysis of 56 paired kidneys, 29% of the recipients with the lower CVP of the pair experienced PNF compared with 11% of their counterparts with higher CVP (p=0.09). Our study indicates that recipient hemodynamics during transplant surgery are major predictors of PNF. Therefore, improving recipient hemodynamics by expansion of the intravascular volume is expected to enhance the results of NHBD kidney transplantations and may enlarge the donor pool by increasing the acceptance of NHBD kidneys.

Redox-active iron released during machine perfusion predicts viability of ischemically injured deceased donor kidneys.

Redox-active iron, catalyzing the generation of reactive oxygen species, has been implicated in experimental renal ischemia-reperfusion injury. However, in clinical transplantation, it is unknown whether redox-active iron is involved in the pathophysiology of ischemic injury of non-heart-beating (NHB) donor kidneys. We measured redox-active iron concentrations in perfusate samples of 231 deceased donor kidneys that were preserved by machine pulsatile perfusion at our institution between May 1998 and November 2002 using the bleomycin detectable iron assay. During machine pulsatile perfusion, redox-active iron was released into the preservation solution. Ischemically injured NHB donor kidneys had significantly higher perfusate redox-active iron concentrations than heart-beating (HB) donor kidneys that were not subjected to warm ischemia (3.9 +/- 1.1 vs. 2.8 +/- 1.0 micromol/L, p = 0.001). Moreover, redox-active iron concentration was an independent predictor of post-transplant graft viability (odds ratio 1.68, p = 0.01) and added predictive value to currently available donor and graft characteristics. This was particularly evident in uncontrolled NHB donor kidneys for which there is the greatest uncertainty about transplant outcomes. Therefore, perfusate redox-active iron concentration shows promise as a novel viability marker of NHB donor kidneys.

Kidney transplantation using elderly non-heart-beating donors: a single-center experience.

Although acceptable outcomes have been reported in both non-heart-beating (NHB) and elderly donors individually, the large pool of elderly NHB donors has not yet been fully utilized. In 1994, we expanded our transplant protocol to include NHB donors aged over 65 years and this study compares the clinical outcomes with regular NHB transplantations. Up to June 2005, 24 patients were transplanted at our center with kidneys from NHB donors aged 65 years or more, whereas 176 patients received grafts from conventional NHB donors during the same period. Grafts from older donors were associated with inferior glomerular filtration rates (29 vs. 44 mL/min after 1 year, p=0.01) and graft survival (52% vs. 68% after 5 years, p=0.19) compared to younger NHB donor grafts, although the difference in graft survival was not statistically significant. Exclusion of older NHB donor kidneys with severe vascular pathology resulted in similar graft survival of older and younger NHB donor kidneys. We conclude that the use of elderly NHB donors in order to expand the donor pool was associated with unacceptable clinical outcomes and cannot be justified without further refinement in their selection, for example, by histological assessment of pretransplant biopsies.