The corticotropin releasing factor system in the kidney: perspectives for novel therapeutic intervention in nephrology.

The adaptation to endogenous and exogenous stress stimuli is crucial for survival but also for the onset of various diseases in humans. Corticotropin releasing factor (CRF) system is the major regulator of stress response and homeostasis. The members of this family of peptides extend their actions also outside CNS to the periphery where they may affect various body systems independently, acting via vagal and/or autocrine/paracrine pathways. In search for peripheral targets, kidney has rarely been studied separately, regarding expression and action of CRF and CRF-related peptides. We reviewed the existing literature concerning expression and action of the CRF system in normal and pathological renal tissue and explored possible clinical implications in nephrology. CRF system components are expressed in the kidney of experimental animals and in humans. The intrarenal distribution is reported to be equally extensive, suggesting a physiological or pathophysiological role in renal function and in the occurrence of renal disease. Urocortins have given multiple interesting observations in experimental models of renal disease and clinical studies, showing robust effects in renal regulation mechanisms. We summarize the relevant data and put them in context, proposing applications with clinical significance in the field of hypertension, diabetic nephropathy, chronic kidney disease, cardiorenal syndrome, and peritoneal dialysis.

Differential effect of baseline adiponectin on all-cause mortality in hemodialysis patients depending on initial body mass index. Long-term follow-up data of 4.5 years.

OBJECTIVES: We sought to investigate the interaction of adiponectin levels and body mass index (BMI) for predicting all-cause mortality in a cohort of hemodialysis (HD) patients. DESIGN: Longitudinal, observational cohort study. SETTING: HD unit. SUBJECTS: Sixty patients (mean age: 64 ± 13 years, 39 men) with end-stage renal disease on maintenance HD followed up for 4.5 years represented the prospective study cohort. INTERVENTION: Associations between baseline plasma adiponectin levels and initial BMI with all-cause mortality were assessed taking into account the assumption of nonlinear correlations. The association between adiponectin, BMI, and serum levels of interleukin-10 (IL-10) and interleukin-6 (IL-6) with survival was determined cross-sectionally. MAIN OUTCOME MEASURE: All-cause mortality. RESULTS: Nonlinear survival modeling showed that there was a U-shaped association of BMI with all-cause mortality, whereas there was an inverse U-shaped association for plasma adiponectin levels. Using a BMI of 24 kg/m(2) as a cutoff, an interaction effect of BMI on the association between adiponectin and mortality was observed (P = .045). In participants with BMI ≥ 24 kg/m(2), each 15 µg/mL increase in plasma adiponectin levels was associated with a decreased hazard of death (hazard ratio: 0.57, 95% CI: 0.32 to 0.99) in unadjusted analysis. In HD patients with BMI < 24 kg/m(2), no significant association was observed between adiponectin and mortality (P = .989). Cross-sectional analysis showed that in the subgroup of patients in whom the protective effect of adiponectin was observed (BMI ≥ 24 kg/m(2)), a positive linear association existed between adiponectin and IL-10 levels (r = 0.345, P = .027) as well as a negative association with IL-6 levels (r = -0.322, P = .040). No association was observed in patients with BMI < 24 kg/m(2), neither with IL-10 nor with IL-6. CONCLUSIONS: Obesity possibly modifies the effect of adiponectin on all-cause mortality in HD patients, thus explaining the published conflicting results in recent literature regarding the association of plasma adiponectin levels and mortality in chronic kidney disease patients.

Impact of long-term cinacalcet, ibandronate or teriparatide therapy on bone mineral density of hemodialysis patients: a pilot study.

BACKGROUND: Insufficient evidenced-based information is available for the treatment of osteoporosis in hemodialysis (HD) patients. METHODS: In 102 HD patients, bone mineral density (BMD) was measured twice 16 ± 3 months apart. In the second BMD measurement 66 of them had a femoral neck (FN) T-score <-2.5. Of these 66 patients, 38 consented to a bone biopsy. Depending on both the bone biopsy findings and parathyroid hormone levels, patients were assigned to treatment groups. Eleven patients with osteitis fibrosa and iPTH >300 pg/ml received cinacalcet, 11 with osteitis fibrosa and iPTH <300 pg/ml received ibandronate, 9 with adynamic bone disease received teriparatide, and 7 with mild abnormalities received no treatment. A third BMD measurement was done after an average treatment period of 13-16 months. We compared the annual percent change of FN and lumbar spine (LS) BMD before and during treatment. RESULTS: FN and LS BMD decreased significantly in the cinacalcet group, with an annual change of 3.6 and 3.4% before treatment to -4.2% (p = 0.04) and -7.7% (p = 0.02) during treatment, respectively. In the teriparatide group, FN and LS BMD increased, although not significantly, with an annual change of -5.4 and -2.6% before treatment to 2.7 and 4.9% during treatment, respectively. In both the ibandronate and the no treatment groups, BMD change rate remained negative during the whole study. CONCLUSIONS: Teriparatide administration improved BMD in HD patients with adynamic bone disease, although these results did not reach statistical significance. In HD patients with osteitis fibrosa, ibandronate did not improve BMD while cinacalcet reduced BMD.

The effect of bicarbonate peritoneal dialysis solutions on cardiac structural and functional alterations.

BACKGROUND: The systemic effects of absorbed glucose degradation products (GDPs) contained within the conventional peritoneal dialysis solutions (cPDS) are largely unknown, while they appear to affect also cardiovascular function. The aim of the present study was to evaluate if the new bicarbonate-based less bioincompatible new peritoneal dialysis solutions ameliorate cardiac structural and functional status as well as the peritoneal net ultrafiltration (UF) and residual renal function. Patients and methods. This is a single centre, prospective cohort study of 12 stable continues ambulatory peritoneal dialysis patients (four women, eight men) mean aged 71.3 ± of 6.01 years and mean peritoneal dialysis (PD) duration 31.9 ± 21.33 months, treated with the usual cPDS (Medital Bieffe®, with increased GDPs, low pH and lactate as a buffer system). The patients changed for a 6-month period to the newer biocompatible PD solutions (BicaVera, Fresenius® low GDPs, normal pH, bicarbonate as a buffer) and at the end of this time, they returned to their previous schema of conventional solutions, for another 6 months. During the study period, the left ventricle ejection fraction (EF), left ventricle end systolic and diastolic diameter (LVESD, LVEDD), left ventricle mass index (LVMI), glyoxal serum and peritoneal concentrations, net UF and 24 h urine volume were repeatedly estimated: at the beginning of the study (T0), after 6 months with the biocompatible solutions (T6) and at the end of study (T12), after the 6-month period using again the cPDS. The UF volume and glyoxal concentrations were estimated at end of a 4 h dwell of an exchange with a PD solution of 2.27 % glucose. RESULTS: There was a statistically significant difference between the mean levels of EF, LVESD, LVEDD, LVMI, UF and glyoxal serum and peritoneal concentrations at the beginning (T0) and in the middle of the study (T6) (for serum glyoxal P = 0.005, for peritoneal glyoxal P = 0.0004, for EF P = 0.0004, for LVESD P = 0.023, for LVEDD P = 0.002, for LVMI P = 0.0005 and for UF P = 0.005) as well as between the mean values in the middle (T6) and at the end of the evaluation period (T12) (for serum glyoxal P = 0.043, for peritoneal glyoxal P = 0.006, for EF P = 0.00009, for LVESD P = 0.012, for LVEDD P = 0.00014, for LVMI P = 0.00013 and for UF P = 0.048). On the other hand, no statistically significant difference was revealed between the T0 and T12 mean values of glyoxal (serum and peritoneal), EF, LVESD, LVEDD, LVMI and UF. During the study period, there was no statistically significant difference in daily urine volume and glomerular filtration rate. CONCLUSIONS: The use of bicarbonate-based PDS induced a statistically significant improvement of left ventricle structure (LVESD, LVEDD and LVMI) and functional (EF) indicators. These beneficial effects on left ventricle in combination with the improvement of net UF may designate a protective role of the newer bicarbonate peritoneal solutions on cardiovascular function morbidity and mortality risk of PD patients.

Impact of C-reactive protein on absolute reticulocyte count in haemodialysis patients: the role of iron status.

BACKGROUND: The exact mechanisms by which the effects of inflammation on erythropoiesis occur are still to be determined. We aimed to examine the relation between C-reactive protein (CRP) and erythropoiesis as quantified by the absolute reticulocyte count (RTC) and the possible effect of iron status on this relationship. METHODS: As part of a study that follows the changes of haematologic parameters after the intravenous (IV) administration of iron in 93 stable haemodialysis (HD) patients, we made a cross-sectional analysis of baseline measurements and an analysis of changes in RTC 1 week after baseline measurements and iron administration. RESULTS: Multiple linear regression analysis revealed that RTC had a positive correlation with CRP; RTC had a negative correlation with reticulocyte haemoglobin content (CHr). An interaction was also found between CRP and CHr in that CRP had a significant relation to RTC only in those patients whose CHr was more than 31.2 pg. At lower values of CHr, the correlation between CRP and RTC was not significant. Five days after the IV administration of 200 mg iron sucrose, a significant increase of RTC was observed, only in those patients with elevated baseline CRP levels who also showed an increase in CHr levels from ≤ 31.2 pg at baseline to ≥ 31.2 pg post-administration, supporting the presence of an independent positive correlation between CRP and RTC when iron is adequate. CONCLUSIONS: It is indicated that, in HD patients, elevated CRP values are associated with increased erythroid production only when CHr is quite satisfactory.

Pivotal role of paricalcitol in the treatment of calcific uremic arteriolopathy in the presence of a parathyroid adenoma.

Calcific uremic arteriolopathy, or calciphylaxis, is a serious and life-threatening complication of end-stage renal disease. Its pathogenesis is not yet fully elucidated and treatment is controversial. In the presence of severe hyperparathyroidism, parathyroidectomy should be considered. We report a case of a woman on maintenance hemodialysis therapy with calciphylaxis and parathyroid adenoma who refused to undergo parathyroidectomy. She was treated successfully with a combination of noncalcium phosphate binders, cinacalcet, and paricalcitol. Subcutaneous plaques disappeared, and the necrotic lesion was healed. Discontinuation of paricalcitol led to an increase in serum parathyroid hormone levels and reappearance of the patient's symptoms, whereas its reintroduction resulted in complete remission of the clinical picture. Paricalcitol, a less calcemic vitamin D analogue, is also a selective vitamin D receptor activator with a number of nonclassic actions (such as inhibition of inflammation and ossification-calcification) that could prove beneficial in cases of calciphylaxis.

Intradialytic Cardiovascular Exercise Training Alters Redox Status, Reduces Inflammation and Improves Physical Performance in Patients with Chronic Kidney Disease.

Redox status (RS) perturbations and inflammation are fundamental features of chronic kidney disease (CKD) that are substantially exacerbated in end-stage renal disease (ESRD). This study aimed at investigating the efficacy of a 6-month intradialytic exercise training program on RS, inflammation and physical performance in patients with ESRD. Twenty hemodialysis (HD) patients (17 males, three females) were randomly assigned to either an intradialytic training (bedside cycling) group (TR; n = 10) or a control group (CON; n = 10) for 6 months. Anthropometrics [body mass and height, body mass index (BMI), body composition], physical performance (VO2peak), functional capacity [North Staffordshire Royal Infirmary (NSRI) walk test, sit-to-stand test (STS-60)], quality of life (short form-36 (SF-36) as well as RS [thiobarbituric acid reactive substances (TBARS), protein carbonyls (PC), reduced (GSH) and oxidized (GSSG) glutathione, GSH/GSSG, total antioxidant capacity (TAC), catalase activity (CAT)] and high-sensitivity C-reactive protein (hs-CRP) were assessed at baseline and after the 6-month intervention. Peak oxygen consumption (VO2peak) increased by 15% only in TR (p < 0.01). Performance in NSRI, STS-60 and SF-36 improved by 4-13% only in TR (p < 0.01). Exercise training reduced TBARS (by 28%), PC (by 31%) and hs-CRP (by 15%), and elevated GSH (by 52%), GSH/GSSG (by 51%), TAC (by 59%) and CAT (by 15%) (p < 0.01). These findings suggest that engagement in chronic intradialytic cardiovascular exercise alters RS, reduces inflammation and improves performance in patients with ESRD.

Comparative in vitro study of different peritoneal dialysis solutions on cytokine production by peripheral blood mononuclear cells.

BACKGROUND/AIMS: Peritoneal dialysis solutions (PDS), new and conventional, do not yet have a clinical biocompatibility profile. We aimed at a comparative laboratory profile based on the effect of PDS on peripheral blood mononuclear cell (PBMC) cytokine release. METHOD: PBMCs from 19 healthy volunteers were incubated at a concentration of 10(6)/ml in fresh PDS and control medium (RPMI 1640), and stimulated or not with 10 microg/ml Escherichia coli lipopolysaccharide. The tested PDS were glucose/lactate 1.5 and 4.25%, glucose/pyruvate 1.0 and 4.0%, icodextrin and amino acid solutions. The initial incubation in culture flasks for 15 min was followed by 1:1 dilution with RPMI and by additional incubation for 22 h as a 'recovery period'. At the end, the supernatants were tested for cytokines IL-6 and TNFalpha by ELISA. RESULTS: The hypertonic glucose solutions, irrespective of the buffer, had the most adverse effect on PBMC cytokine release. The icodextrin and amino acid solutions seemed close to the isotonic glucose PDS. The substitution of pyruvate for lactate buffer seemed to offer an advantage only for the hypertonic glucose-based solutions. CONCLUSIONS: Icodextrin and amino acid solutions seem to offer an advantage only compared to hypertonic glucose PDS.

Auditory brainstem responses in patients under treatment of hemodialysis.

This study evaluated the effects of end stage chronic renal failure (CRF) on auditory function and changes in auditory function following a single session of hemodialysis. The experimental group included 31 patients with end-stage renal failure on chronic hemodialysis. The control group consisted of 31 healthy volunteers. The patients were examined prior to and following a session of hemodialysis. Measurements included pure tone audiometry, tympanometry and acoustic reflex measurements, auditory brainstem responses (ABR), and blood now chemistry parameters. Controls underwent the same test battery, with the exception of biochemical and hematological assessment. Prior to hemodialysis sessions, all ABR latencies except interpeak latency I-III were significantly prolonged in the experimental group. A comparison between controls and the experimental group following hemodialysis indicated that wave V absolute latency and interpeak latencies III-V and I-V were significantly prolonged in the slow repetition rate paradigm. In the fast repetition rate, absolute latencies of waves I and V and III-V interpeak latencies were prolonged in the experimental group. Comparison of ABR recordings prior to and following hemodialysis showed overall significant difference between the measures. Post hoc analysis showed a significant improvement in wave I and V latencies in the slow repetition rate and wave V latency in the fast repetition rate. This study showed that neural conduction along the auditory pathway is delayed in patients with end stage CRF as compared to healthy subjects. Dialysis sessions improve overall neural auditory function. However, patients with end stage CRF show delayed conduction even after a session of hemodialysis.

Efficacy of intravenous methoxy polyethylene glycol-epoetin beta administered every 2 weeks compared with epoetin administered 3 times weekly in patients treated by hemodialysis or peritoneal dialysis: a randomized trial.

BACKGROUND: C.E.R.A. (methoxy polyethylene glycol-epoetin beta), a continuous erythropoietin receptor activator, was developed to provide stable control of hemoglobin (Hb) levels at extended administration intervals in patients with chronic kidney disease. We examined its efficacy for Hb level correction when administered once every 2 weeks in erythropoiesis-stimulating agent-naive dialysis patients. STUDY DESIGN: Open-label, multicenter, randomized, parallel-group, phase 3 study. SETTING & PARTICIPANTS: Dialysis patients (age >or= 18 years). INTERVENTION: Patients (n = 181) were randomly assigned (3:1) to receive intravenous C.E.R.A. once every 2 weeks or epoetin 3 times weekly. OUTCOMES & MEASUREMENTS: The primary end point was Hb level response rate (increase in Hb level >or= 1 g/dL [10 g/L] versus baseline and Hb level >or= 11 g/dL [110 g/L] without blood transfusion during the 24-week correction period) in the intent-to-treat population. RESULTS: Hb response rates (intent-to-treat population) were 93.3% with C.E.R.A. and 91.3% with epoetin. Similar results were found in the per-protocol population. Peak mean Hb levels were 12.28 +/- 1.13 (SD) g/dL (122.8 +/- 11.3 g/L) with C.E.R.A. and 12.19 +/- 1.24 g/dL (121.9 +/- 12.4 g/L) with epoetin. Mean change in Hb levels from baseline to the end of the correction period were 2.70 +/- 1.45 g/dL (27 +/- 14.5 g/L) with C.E.R.A. and 2.56 +/- 1.31 g/dL (25.6 +/- 13.1 g/L) with epoetin. Both treatments were generally well tolerated. LIMITATIONS: Open-label study design, 3:1 randomization, limited peritoneal dialysis population, descriptive statistics, and lack of formal prespecified comparison to epoetin. CONCLUSIONS: Intravenous C.E.R.A. once every 2 weeks may be as safe and effective as 3-times-weekly epoetin for correcting anemia in dialysis patients. These results show the utility of intravenous C.E.R.A. administered once every 2 weeks in erythropoiesis-stimulating agent-naive dialysis patients.

The value of serum antilipoarabinomannan antibody detection in the diagnosis of latent tuberculosis in hemodialysis patients.

BACKGROUND: The risk for tuberculosis (TB) reactivation in hemodialysis (HD) patients is increased, and screening for latent TB is recommended. The tuberculin skin test (TST) is inaccurate because of the high incidence of anergy in skin testing in HD patients and its inability to differentiate latent from eradicated TB infection. In this study, use of serum antilipoarabinomannan (anti-LAM) antibody detection for the diagnosis of latent TB in a dialysis population was evaluated. METHODS: Seventy-four HD patients never treated for TB composed the first group. Forty-eight healthy volunteers never treated for TB served as controls. Twenty-one TST-positive renal transplant candidates on dialysis therapy who had completed preventive anti-TB treatment formed a third group. The TST (using the Mantoux method) and anti-LAM test (using an immunochromatographic assay) were performed in all subjects participating in the study. RESULTS: In the first group, a strong association was detected between results of the TST and anti-LAM test (P < 0.0001, chi-square test). A similar association was found in the second group. In the group of HD patients treated for TB, a positive TST result and negative anti-LAM test result was a constant finding. CONCLUSION: The association between the TST and anti-LAM test in HD patients suggests that the anti-LAM test could be a useful tool for diagnosing latent TB. The absence of anti-LAM antibodies in anti-TB-treated HD patients suggests that immune response to lipoarabinomannan lacks long-lasting memory. A negative anti-LAM test result might reflect the absence of latent TB, even in patients with a positive TST result.

Peritoneal catheters and related infections.

Catheter related infectious complications (exit-site infections, tunnel infections, and peritonitis) remain the major reasons for technique failure during the three decades since, continuous ambulatory peritoneal dialysis (CAPD) treatment has been first established. Despite improvements in catheter's survival rates, catheter related complications result in an increase in the cumulative patients' morbidity and often leading to the catheter removal. The ideal catheter provides reliable and rapid dialysate flow rates without leaks or infections. Among several types, the double-cuff straight Tenckhoff catheter, developed in 1968, is still the most widely used, although its use is decreasing in favour of swanneck catheters. Although there are only few well-designed trials comparing catheters and catheters related infectious complications, controlling for all other important variables, no difference in these complications among the main types of catheters was seen. The single cuff catheters have been associated with a shorter survival rate and time to the first peritonitis episode than the double-cuff catheters. Also exit-site infections were found to be more frequent and significantly more resistant to treatment with single-cuff compared to double-cuff ones. Finally, better results have been reported with the latest developed presternal peritoneal dialysis catheter both regarding survival rates and exit-site infection and peritonitis rates. Recently a renewed interest in continuous flow peritoneal dialysis stimulated inventions of imaginative, double-lumen catheters since a suitable peritoneal access is a sine qua non condition for the development of this new technique of peritoneal dialysis.

Association of Plasma Adiponectin and Oxidized Low-Density Lipoprotein with Carotid Intima-Media Thickness in Diabetic Nephropathy.

AIMS: We sought to determine the association between levels of adiponectin and oxidized low-density lipoprotein (ox-LDL) in patients with diabetic nephropathy as well as their effect on carotid intima-media thickness (cIMT). METHODS: Adiponectin and ox-LDL were determined in 25 diabetic patients without nephropathy and 94 patients at different stages of diabetic nephropathy including subjects on hemodialysis. cIMT was measured using real-time B-mode ultrasonography. RESULTS: Plasma adiponectin levels increased significantly with severity of diabetic nephropathy (P = 0.002), on the contrary to ox-LDL which decreased with disease severity (P < 0.001). cIMT was significantly higher at late stages of diabetic nephropathy compared with early stages (P = 0.022). Adiponectin was a significant negative predictor of ox-LDL levels (ß = -5.45, P = 0.023), independently of confounding factors. There was no significant correlation between cIMT and adiponectin or ox-LDL either in the total sample population or according to disease staging. Cluster analysis showed that patients with the highest cIMT values, highest levels of adiponectin, and lowest levels of ox-LDL were included in one cluster and all assigned to stage 5 of diabetic nephropathy. CONCLUSIONS: There was no significant association between adiponectin or ox-LDL and cIMT and, therefore, other factors affecting this surrogate marker of cardiovascular disease in diabetic nephropathy should be sought.

Vascular access for hemodialysis: postoperative evaluation and function monitoring.

Vascular access (VA) survival is a crucial issue associated with morbidity and mortality of patients undergoing maintenance hemodialysis. The development of stenosis is the major factor that leads to VA failure. Strategies for early detection of lesions within a VA system before serious complications arise are therefore crucial. The implementation of a VA surveillance program could lead to timely detection of VA dysfunction and referral for correction, reduction in central venous catheter use and decrease in hospitalization and VA-related cost. Suggested methods for arteriovenous fistulae and grafts surveillance include blood flow measurement, static pressure evaluation and duplex ultrasonography. Physical examination is an accepted method in contrast to nonstandardized dynamic pressure measurement for grafts. Access recirculation (not urea based) and dynamic pressure measurements are accepted methods for fistulae. Decreasing URR or Kt/V (otherwise unexplained) and increased (negative) arterial pressure in the dialysis machine are methods of limited sensitivity and specificity for both fistulae and grafts. Measurement of access blood flow has been proposed as the gold standard for the screening of all types of VA. Access flow can be measured by various techniques which are direct or indirect. Several studies about VA surveillance programs have demonstrated conflicting results. Larger, randomized controlled trials need to be carried out in order to clarify whether surveillance programs are necessary and which is the best surveillance strategy for each type of VA.

Validation of a new risk score to predict contrast-induced nephropathy after percutaneous coronary intervention.

Contrast-induced nephropathy (CIN) is a frequent, potentially lethal complication of percutaneous coronary interventions (PCIs). We prospectively validated the diagnostic performance of a simple CIN risk score in a large multicenter international cohort of patients who underwent PCI. About 2,882 consecutive patients treated with elective or urgent PCI were enrolled. A simple CIN risk score was calculated for all patients by allocating points according to a prespecified scale (pre-existing renal disease = 2; metformin use = 2; previous PCI = 1; peripheral arterial disease = 2; and injected volume of contrast medium ≥300 ml = 1). CIN was defined as an increase, compared with baseline, of serum creatinine by ≥25%, or by ≥0.5 mg/dl, 48 hours after PCI. CIN occurred in 15.7% of the study population. The predictive accuracy of the CIN risk score was good (c-statistic 0.741, 95% confidence interval 0.713 to 0.769). Receiver-operating characteristic analysis identified a score of ≥3 as having the best diagnostic accuracy. Examination of the performance of the proposed risk score using different definitions of CIN yielded a robust predictive ability. The score exhibited good discrimination (area under the curve ≥0.700) across all predefined subgroups of the study population. Compared with 2 previously published risk scores for CIN, our score demonstrated higher discriminative ability and resulted in a net reclassification improvement and an integrated discrimination improvement (p <0.001). In conclusion, the new risk score can easily be applied in the setting of urgent or elective PCI, allows for robust risk assessment and offers the potential to improve the peri-interventional management of patients at risk for CIN.

Development of an easily applicable risk score model for contrast-induced nephropathy prediction after percutaneous coronary intervention: a novel approach tailored to current practice.

BACKGROUND: Several risk factors for contrast-induced nephropathy (CIN) after percutaneous coronary intervention (PCI) have been identified. The cumulative effect of these risk factors on renal function has been assessed with the development of risk score models in a number of studies. However, concerns were raised that estimates of the risk attributable to individual factors may be unreliable. We sought to develop a simple risk score for developing CIN after PCI irrespective of use of prophylactic measures and also capturing the effect of pre-intervention medication and presence of various co-morbidities. METHODS: Consecutive patients treated with elective or urgent PCI at our cardiac catheterization laboratory were enrolled (derivation cohort n = 488, validation cohort n = 200). CIN was defined as increase ≥ 25% and/or ≥ 0.5 mg/dl in serum creatinine at 48 h after PCI vs baseline. Multivariable logistic regression analysis was then performed to identify independent predictors of CIN (pre-existing renal disease, metformin use, history of previous PCI, peripheral arterial disease and ≥ 300 ml of contrast volume). RESULTS: The incidence of CIN in the development cohort was 10.2% with a significant trend across increasing score values (p < 0.001). The model demonstrated good discriminating power (c-statistic 0.759) and excellent calibration (calibration slope 0.91). The model was validated internally by bootstrapping in 1000 samples (c-statistic 0.753) and in a cohort of 200 patients (c-statistic 0.864) demonstrating stable performance. CONCLUSIONS: The proposed risk score is easily applicable and allows for practically simple risk assessment compared to other published scores while at the same time overcomes drawbacks of previous model designs.