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Estimated glomerular filtration rate (eGFR) methods are not sufficiently reliable in renal transplant recipients (RTR) and should be replaced by iohexol plasma clearance measurement. However, this method has poor availability in health centers. The aim of our study was to develop a high-performance liquid chromatography (HPLC) method for plasma iohexol measurement in routine practice and to evaluate its plasma clearance as a reference of GFR. We developed an HPLC method using UV detection. We evaluated sample storage conditions to provide recommendations for routine practice. Then, we compared GFRbased on plasma iohexol clearance (GFR-iohexol) to eGFR using modification of diet in renal disease, Cockcroft and Gault, and CDK-EPIequations in 40 RTR. The method was validated over a concentration range of 15-300 μg/l. Excellent linearity (r > 0.998), inter- and intraday precision (CV < 3.3%), and accuracy (>96.8%) were complied with ICH guidelines. We also demonstrated excellent samples stability (9 days). Although eGFR methods are not references in RTR, we found a correct concordance between eGFR and GFR-iohexol in our population. To conclude, our method is simple, rapid, accurate, and reliable for routine clinical and research use especially in RTR., (© 2012 Wiley Periodicals, Inc.)

Pulse pressure and urinary albumin excretion were recently identified as risk factors of new-onset diabetes after renal transplantation (NODAT), suggesting that microvascular injury may be implicated in NODAT. However, the relationship between of microvascular injury and NODAT is unknown. In the present long-term (median follow-up: 5.7years; observation period: 4908 patient-years) retrospective study in 656 renal transplant recipients, the association between baseline renal resistance index (RI, used as a marker of widespread microvascular damage) and the incidence of NODAT was assessed. The incidence of NODAT was 11.2% and 14.6% at 5 and 10years, respectively, after transplantation. RI at 3months was a risk factor for NODAT [hazard ratio (HR) per 0.1: 2.19 (1.55-3.09), P<0.0001]. RI >0.75 (vs. 0≤0.75) was a potent a predictor of NODAT [HR: 3.29 (1.91-5.67), P<0.0001], even after adjustments [HR: 3.29 (1.50-7.24), P=0.0030] on age, weight, glucose, nephropathy, and arterial pressure. Similar results were observed when RI was measured at 1month [HR per 0.1:1.74 (1.33-2.27), P<0.0001] and 12months [HR per 0.1:1.74 (1.33-2.27), P<0.0001] after transplantation. High RI early after renal transplantation is a long-term risk factor for NODAT, and could be used to refine the individual risk of NODAT., (© 2012 The Authors. Transplant International © 2012 European Society for Organ Transplantation.)

The clinical merit of surveillance kidney graft biopsies remains controversial. A retrospective, multicenter analysis evaluated 12-month surveillance biopsies (SB, 154 patients) versus no SB (NSB, 138 patients (11 with diagnostic biopsy)) in patients >18 months posttransplant with estimated GFR (eGFR) ≥30 mL/min. The primary objective was to describe renal function at 18 months post-transplant in patients with or without SB at month 12. Globally, most recipients in both cohorts were at low immunological risk (<10% of patients with PRA ≥30%). The immunosuppressive regimen remained unchanged following more than half of SB that exhibited chronic lesions (18/33, 54.5%). Mean (SD) eGFR at month 18 (primary endpoint) was 56 (19) mL/min/1.73 m² with SB and 54 (15) mL/min/1.73 m² with NSB (P = 0.48). In the SB group, slight nonspecific changes were observed in 51 cases, rejection (acute or chronic) in 6 cases, CNI-related toxicity in 15 cases, recurrence of initial disease in two cases, and interstitial fibrosis/tubular atrophy (IF/TA) in 83 cases (71.6%), of which 35 cases (30.2%) were grade II/III lesions. eGFR <50 mL/min/1.73 m² at month 6 predicted IF/TA grade II or III (OR 3.85, 95% CI 1.64, 9.05, P < 0.002). SB at 12 months posttransplant did not prompt significant modification of immunosuppression, and no renal benefit was observed.

Background: The predictive value of doubling of serum creatinine (DSC) has never been assessed in renal transplantation. We evaluated it in terms of its use for clinical trials, cost-effectiveness studies, and individual patients., Methods: Retrospective longitudinal study in 896 renal transplant recipients., Results: Death-censored graft loss occurred in 133 patients, during follow-up (up to 21 years). DSC was a risk factor for graft loss; however, the relative risk was different in patients with glomerular filtration rate less than 40 vs. more than or equal to 40 mL/min (hazard ratio: 14.5 [95% confidence interval: 7.4-28.4] vs. 47.8 [28.4-80.6], P=0.0051). Parameters influencing creatinine value (weight, age, sex) did not modify DSC's predictive value. The use of the composite endpoint DSC or death-censored graft loss instead of death-censored graft loss alone in clinical trials would reduce sample size by 7.1% to 9.0%. The annual probability of DSC to graft loss transition decreased from 76% (follow-up <1 year) to 5% (follow-up ≥10 years). Median graft half-life after DSC was 10 months [95% confidence interval: 6-18] but varied with increasing time to DSC (<1 year: 1 month [0.5-6]; 3-4.9 years: 15 months 5/67) and reference creatinine (<130 μmol/L: 3 months 2/6); ≥130 μmol/L: 25 months 15/37)., Conclusions: DSC may be adequately used to refine the risk of death-censored graft loss for individual patients. However, the use of DSC as an endpoint in clinical trials marginally affects sample size, and the probability of DSC to graft loss transition is not constant, which limits the use of DSC in cost-effectiveness analyses of renal 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.

Acquired cutis laxa is an uncommon disorder sometimes associated with monoclonal gammopathy and multiple myeloma, although the mechanism of this link is unclear. We report here a case of a 34-year-old man with generalized acquired cutis laxa and monoclonal light chain disease with renal and neurological involvement. Electron microscopy examination of a skin sample revealed shortened and fragmented elastic fibres in the reticular dermis and normal collagen bundles. Immunogold labelling revealed anti-lambda antibodies closely bound to the microfibrillar component of elastic fibres, thus supporting a causal relationship between monoclonal gammopathy and the changes in skin elasticity.

New-onset diabetes after transplantation (NODAT) is a growing concern in transplantation. All modifiable risk factors are not yet identified. We assessed the relationship between baseline clinical and biochemical parameters and NODAT. Eight-hundred and fifty-seven in-Caucasian renal transplant recipients were included. Charts were individually reviewed. The follow-up was 5.3 years (ranges: 0.25-20.8; 5613 patient-years). The incidence of NODAT was 15.0%, 18.4% and 22.0% at 10, 15 and 20 years following transplantation. Age, body mass index (BMI), glucose (all P < 0.0001) and triglycerides [hazard ratio (HR) per 1 mmol/l: 1.44 [1.17-1.77], P = 0.0006] were potent risk factors whereas steroid withdrawal (HR: 0.69 [0.47-1.01], P = 0.0601) reduced the risk. As compared to cyclosporine, sirolimus (HR: 3.26 [1.63-6.49], P = 0.0008) and tacrolimus (HR: 3.04 [2.02-4.59], P < 0.0001) were risk factors for NODAT. The risk of NODAT was comparable for sirolimus (HR: 2.35 [1.06-5.19], P = 0.0350) and tacrolimus (HR: 2.34 [1.46-3.75], P = 0.0004) after adjustments on age, BMI, glucose and steroid withdrawal; however, unlike sirolimus, tacrolimus remained significant after adjustment on triglycerides. The risk of NODAT appeared similar, but its pathophysiology seemed different in sirolimus- and tacrolimus-treated patients; this observation needs confirmation. However, main independent risk factors were age, BMI, initial glucose and triglycerides.