None of these formulas seems to be able to safely substitute for inulin clearance. In clinical trials, renal graft function should be preferably assessed using a reference method of GFR measurement.

After organ transplantation, susceptibility to cancer is multifactorial, especially for skin carcinomas. Risk factors may include genetic susceptibilities, such as the control of cytokine production. Interleukin-10 is a cytokine that is implicated in tumorigenesis, and it has been shown that polymorphisms in its gene promoter correlate with differential amounts of production. The aim of this study was to investigate a possible association between interleukin-10 gene promoter polymorphisms and the occurrence of skin carcinomas after renal transplantation. Seventy kidney transplant recipients who developed a squamous cell carcinoma or a basal cell carcinoma were examined for polymorphisms in the interleukin-10 gene promoter using polymerase chain reaction based methods. Single base pair mutations were studied at positions -1082, -819, and -592. These patients were compared to 70 healthy controls and to 70 matched renal transplant recipients without cancer. The interleukin-10 secretion capability was tested in a subgroup of 40 of these patients by in vitro stimulation of peripheral mononuclear cells. Interleukin-10 genotypes and haplotypes were differently distributed in kidney transplant recipients who developed a skin carcinoma, but especially a squamous cell carcinoma, with an increased frequency of the GCC haplotype and a decreased frequency of the ATA haplotype. Subsequently, we found a shift in the predicted phenotypes from the low production phenotype to the high production phenotype. Secretion of interleukin-10 was strongly correlated to the production predicted phenotype, and tended to be higher in patients who developed a squamous cell carcinoma than in the others. These results indicate that interleukin-10 gene polymorphisms and interleukin-10 production capability may contribute to the development of skin squamous cell carcinomas after renal transplantation.

The kidney disease outcomes quality initiative (K/DOQI) guidelines introduced a classification of chronic kidney disease (CKD) based on the level of kidney function. In order to predict the glomerular filtration rate (GFR), they specifically recommended the use of the modification of diet in renal disease (MDRD) study and Cockcroft-Gault (C-G) equations.Since the performance of these estimates has been questioned, we sought to determine whether these recommendations might be applicable in renal transplantation.Following the K/DOQI methodology, we compared the GFR estimated by the MDRD and C-G equations with 476 inulin clearances performed in 284 renal transplant recipients.Even though the MDRD equations provided a better prediction than C-G formula, none of them reached the level of accuracy required by the K/DOQI standards. At least, 25% of the calculated GFR gave a prediction beyond 30% of the corresponding inulin clearance value. In addition, when classified according to their predicted GFR, less than two-thirds of the transplant patients turned out to be assigned to the correct stage of CKD.We conclude that, in renal transplantation, the predictive performance of both C-G and MDRD study equations appears to be particularly impaired and may potentially compromise the validity of the K/DOQI guidelines if implemented in their current form.

In general nephrology, HCV infection has been associated with type I membranoproliferative glomerulonephritis (MPGN type I) associated with cryoglobulinaemia. In a cohort of 399 renal transplantation (RT) recipients, 117 of whom (29%) were HCV-positive, we selected all patients diagnosed as having membranous GN or type I MPGN by graft biopsy. The prevalence of MGN was 16/399 (4%) with three recurrences, and 13 de novo cases. Only 5/16 (31%) were HCV+, not different from the general RT population. Five patients had an outcome of graft failure after 43 months. Conversely, there were 15 cases of type I MPGN (two recurrences, 13 de novo) but with eight HCV+ recipients (53%, P = 0.02). Considering only the French patients, prevalence was 44% vs 12% in the French RT population (P = 0.006). Eight patients had graft rejection after 59 months (five HCV+). In this type I MPGN subgroup, there were two positive cryoglobulins, two rheumatoid factors and four hypocomplementaemias. In conclusion, there is a clear association between HCV infection and the occurrence of type I MPGN in the allograft in renal transplantation, with terminal renal failure as an outcome.

Idiopathic membranous nephropathy (IMN) has a strong association with the major histocompatibility complex HLA B8DR3(17)DQ2 haplotype. The tumor necrosis factor (TNF)A gene is located within the major histocompatibility complex region on chromosome 6. We have studied the influence of two functional polymorphisms; the -308 (promoter region) and the TNFd microsatellites on initiation and/or progression of IMN. This was a case-control study comparing data from 100 Caucasians patients (67 male subjects; 67%) with IMN to 232 Caucasians local controls (171 male subjects; 74%). We have analyzed genotypes and alleles distributions and the role of these polymorphisms in disease progression towards end-stage renal failure or patient death. For -308 TNFA polymorphism, distribution of genotypes was significantly different between IMN and controls (chi(2)=16.25; P=0.0003): the A2 allele frequency was 28.0% in IMN vs 15.3% in controls (chi(2)=14.57; P=0.0001). For TNFd polymorphism, alleles distribution (from d1 to d7) was also significantly different between IMN and controls (chi(2)=56.74; P<0.0001) with both diminished d3 allele frequency (chi(2)=27.30; P<0.0001; Pc=0.001) and increased d2 allele frequency (chi(2)=29.95; P<0.0001; Pc=0.001) in IMN. We could not isolate any significant and independent influence of these different genotypes on IMN disease progression. The TNFA2 and TNFd2 alleles were strongly associated with occurrence/initiation of IMN and should be considered as susceptibility genes for this disease.