Patricia Berthoux

Predicting glomerular filtration rate in kidney transplantation: are the K/DOQI guidelines applicable?

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.

Hypertension after renal transplantation and polymorphism of genes involved in essential hypertension: ACE, AGT, AT1R and ecNOS

BACKGROUND Arterial hypertension (HT), secondary to cyclosporine A (CsA) used as main immunosuppressive treatment in renal transplantation (RTx), is very frequent (70%), usually severe and explained mostly by vasoconstriction of the glomerular afferent arteriole with secondary sodium and water retention. MATERIAL AND METHODS In a retrospective study, we have analyzed 294 consecutive recipients receiving a first renal cadaveric allograft and all treated with CsA (the majority with triple therapy). We studied, by molecular biology, the polymorphism of genes previously implicated in essential HT such as: angiotensin-converting enzyme (ACE: II, ID and DD), angiotensinogen (AGT: MM, MT and TT), angiotensin II type 1 receptor (AT1-R: AA, AC and CC) and endothelial constitutive nitric oxide synthase (ecNOS: aa, ab and bb), and correlated the data to the prevalence and severity of post-Tx HT. This cohort included 195 (66%) males and 99 females with a mean age of 42 years at time of Tx. The presence and severity of post-Tx HT were indicated by initial persistent blood pressure over 140/90 mmHg with the need for at least one anti-hypertensive drug and by the number of anti-HT medications required to achieve its control. RESULTS The distribution of the specific alleles and genotypes for ACE, AGT, AT1-R, and ecNOS was not different in transplant recipients compared to 181 controls. At 5 years post-Tx, the prevalence of HT was 72% (169 out of 235) among functioning grafts. There was no significant difference for ACE, AGT, AT1R and ecNOS genotypes distribution between hypertensive vs non-HT recipients. The number of anti-hypertensive drugs prescribed was not different among ACE, AGT, and AT1-R genotypes. However, the a allele and the non-bb genotype (aa + ab) for ecNOS were significantly (p = 0.001) associated with a less severe HT, needing fewer anti-HT drugs. At 10 years post-Tx, the HT prevalence remained high 78% (67 out of 86) among functioning Tx. However, the limited numbers did not allow further correlation. CONCLUSIONS This study produced mainly negative results except for ecNOS-a allele, which seems to protect against severe hypertension. The explanation remains speculative but probably relates to the known cyclosporine-induced upregulation of ecNOS gene and enzyme activity.

Membranoproliferative Glomerulonephritis with Subendothelial Deposits (Type 1) Associated with Hepatitis G Virus Infection in a Renal Transplant Recipient

Background: Infection with hepatitis B virus (HBV) or hepatitis C virus (HCV) is a well-known etiology for membranoproliferative glomerulonephritis (MPGN) with subendothelial deposits (MPGN type 1). Material and Methods: The newly discovered hepatitis G virus (HGV) is currently under active investigation. We report the first case of de novo MPGN type 1 associated with HGV infection in a young male renal transplant recipient who manifested glomerulonephritis (GN) with proteinuria 7 years after transplant, and whose original disease was chronic obstructive pyelonephritis secondary to nephrolithiasis. Results: Serum markers for HBV and HCV infections were negative. HGV infection was detected by specific double-nested reverse transcriptase-polymerase chain reaction (RT-PCR) in sera (positive HGV viremia) 2.5 years after renal transplantation. By specific in situ RT-PCR, the presence of the HGV genome was detected in peripheral blood mononuclear cells and in the kidney biopsy (glomeruli and tubules), but not in the liver. Conclusion: This report adds new information on the role of HGV infection in the occurrence of de novo GN (MPGN type 1) in renal transplantation.

Transporter‐associated with antigen processing genes in primary IgA glomerulonephritis

Summary: Transporter‐associated with antigen processing (TAP1 and TAP2) gene products are involved in the transport/processing of self‐peptides from cytosol into endoplasmic reticulum (ER). In ER, these peptides associate with human leucocyte antigen (HLA)‐class I molecules for further presentation at cell surface. Deficient processing and/or presentation could lead to altered self‐tolerance resulting in autoimmunity. We studied TAP1 and TAP2 genes and genotypes frequencies in 49 controls and in 101 patients with primary IgA nephritis (IgAN). the patients were divided into two groups: 45 patients with end‐stage renal failure (ESRF) and 56 patients with normal kidney function (NKF). DNA was extracted from peripheral blood and amplified by double amplification refractory mutation system‐polymerase chain reaction (ARMS‐PCR) using appropriate primers for the two point‐mutations on TAP1 genes and for the three point‐mutations on TAP2 genes, which are the basis of TAP polymorphism. We have found a weak association between TAP2‐p379‐VAL/ILE genotype and total‐IgAN (24%vs 12% in controls; P= 0.05). However, the analysis of a subgroup of IgAN patients bearing HLA‐B35 antigen, a former poor prognosis marker, disclosed an association between the TAP2‐1993Ntd‐Guanine variant (coding for TAP2‐p665‐ALA): 31% in B35‐ESRF‐IgAN subgroup vs 6% in controls (P=0.04) and 13% in B35‐NKF‐IgAN (P=NS). the complexity of immunogenetic studies in IgAN is further increased by the existence of two opposite pathological subgroups: normal glomerular basement membrane (GBM) thickness vs thin‐GBM. There was a complex relation in IgAN between this TAP2 variant and the following parameters: ESRF, HLA‐B35, and normal‐GBM. Further investigations are therefore needed.