[Renal, vascular and urological variations and abnormalities in living kidney donor candidates]. / Variations et anomalies néphrologiques, vasculaires et urologiques chez les candidats au don vivant rénal.

INTRODUCTION: The aim of this study was to determine the prevalence of anatomic variations (renal, vascular and urological) and acquired renal pathologies in living kidney donor candidates (LKDC). METHODS: This is a retrospective study of all LKDC referred to our center between April 2003 and September 2014. Of the 491 LKDC, 189 were initially excluded for medical reasons (n=140) or others reasons (n=49), without undergoing a radiological assessment. In total, 302 had a radiological assessment (angio-CT or MRI) in anticipation of the donation and 226/302 (73.5%) could donate a kidney. RESULTS: One or more anatomical variations and/or acquired abnormalities were observed in 178/302 (58.9%) of the LKDC. The most frequent were arterial variations or abnormalities (multiple arteries, fibrodysplasia, aneurysms, stenosis≥70%) which where observed in 39.3% of the LKDC, followed by the venous abnormalities (27.8%). Kidney stones were observed in 5.6% of the LKDC and the urinary abnormalities (duplication/ureteral bifidity) were found in 3% of the LKDC. No malignant tumour was diagnosed, while 4 benign tumours (1.3%) were identified, and one of them required additional investigations. CONCLUSION: We found a high prevalence of anatomical variations and acquired abnormalities in a population of LKDC. However, these findings resulted in the exclusion of only 4% of the candidates, because they did not contraindicate the donation or, in most of cases, the contralateral kidney could be used. LEVEL OF EVIDENCE: 3.

Use of Intraoperative Duplex Ultrasound and Resistance Index Reduces Complications in Living Renal Donor Transplantation.

BACKGROUND: The treatment of choice in end-stage renal disease is transplantation. Hemodynamic disturbances can evoke graft loss, while early ultrasound identification of vascular problems improves outcome. The aim of this study was to identify differences in postoperative complications with and without systematic intraoperative Doppler ultrasound use. METHODS: The primary outcome was the postoperative rate of complications and the secondary aim was to find a predictive resistance index cut-off value, which would show where surgical reintervention was necessary. Over a 10-year period, 108 renal transplants were performed from living donors at our institution. In group 1 (n = 67), intraoperative duplex ultrasound and intraparenchymatous resistance index measurements assessed patients, while in group 2 (n = 41), no ultrasound was performed. RESULTS: There were no intergroup differences in the overall postoperative complication rate or in benefit to graft or patient survival with Doppler use. However, significantly more vascular complications (10% vs 0%, P = .02) and more acute rejections (37% vs 10%) occurred in group 2 than in group 1. Therefore, an intraoperative cut-off value of the resistance index 0.5 was proposed to justify immediate surgical revision. CONCLUSIONS: This is the first report demonstrating benefits of systematic intraoperative Doppler ultrasound on postoperative complications in renal transplantation from living donors. Our results support surgical revision with a resistance index <0.5.

CRTC2 polymorphism as a risk factor for the incidence of metabolic syndrome in patients with solid organ transplantation.

Metabolic syndrome after transplantation is a major concern following solid organ transplantation (SOT). The CREB-regulated transcription co-activator 2 (CRTC2) regulates glucose metabolism. The effect of CRTC2 polymorphisms on new-onset diabetes after transplantation (NODAT) was investigated in a discovery sample of SOT recipients (n1=197). Positive results were tested for replication in two samples from the Swiss Transplant Cohort Study (STCS, n2=1294 and n3=759). Obesity and other metabolic traits were also tested. Associations with metabolic traits in population-based samples (n4=46'186, n5=123'865, n6>100,000) were finally analyzed. In the discovery sample, CRTC2 rs8450-AA genotype was associated with NODAT, fasting blood glucose and body mass index (Pcorrected<0.05). CRTC2 rs8450-AA genotype was associated with NODAT in the second STCS replication sample (odd ratio (OR)=2.01, P=0.04). In the combined STCS replication samples, the effect of rs8450-AA genotype on NODAT was observed in patients having received SOT from a deceased donor and treated with tacrolimus (n=395, OR=2.08, P=0.02) and in non-kidney transplant recipients (OR=2.09, P=0.02). Moreover, rs8450-AA genotype was associated with overweight or obesity (n=1215, OR=1.56, P=0.02), new-onset hyperlipidemia (n=1007, OR=1.76, P=0.007), and lower high-density lipoprotein-cholesterol (n=1214, ß=-0.08, P=0.001). In the population-based samples, a proxy of rs8450G>A was significantly associated with several metabolic abnormalities. CRTC2 rs8450G>A appears to have an important role in the high prevalence of metabolic traits observed in patients with SOT. A weak association with metabolic traits was also observed in the population-based samples.

[Transition in kidney transplantation]. / Transition en transplantation rénale.

Transition from pediatric to adult care in renal transplantation has emerged as a critical step in the life of a young kidney recipient. During this phase, young patients are faced with the physiological and psychological changes associated with adolescence that can lead to non-compliance and potentially graft loss. To date, there is not a unique accepted model of transition, however it has been proved that the presence of a multidisciplinary team including specialists in adolescent management and in the transition from pediatric to adult transplant care is beneficial during this at-risk phase. The goal of this team is to ensure a progressive transition of the patients according to a precise plan and time line.

[Renal glucosuria]. / Glucosurie rénale.

The occurrence of glucosuria in the absence of hyperglycemia is distinctive for renal glucosuria. SGLT2 mutations provoke familial renal glucosuria characterized by persistent glucosuria in the absence of any other renal tubular dysfunction. Renal glucosuria associated with others proximal tubular dysfunctions points to Fanconi syndrome. This generalized dysfunction of proximal tubule needs to be treated and may progress regarding its aetiology to chronic renal failure. The development and study of models of Fanconi syndrome has recently contributed to a better knowledge of the mechanisms implicated in the tubular transport of glucose and low-molecular-weight-proteins. This article reviews these recent developments.

Acute norovirus-induced agranulocytosis in a pediatric kidney transplant recipient.

Norovirus (NoV) infection is usually limited to the gastrointestinal (GI) tract. However, in immunocompromised patients, this infection might lead to severe life-threatening complications. We herein describe a pediatric kidney transplant patient who presented with an acute NoV infection complicated by febrile agranulocytosis that resolved with improvement of her GI illness. This unusual presentation has not been described before, to our knowledge. The aim of this article is to highlight the sometimes dramatic clinical presentation of NoV infection in immunosuppressed patients, and the importance of including this infection in the differential diagnosis of neutropenia in that specific population.

Absence of mTOR Inhibitor Effect on Hepatic Cyst Growth: A Case Report of a Kidney Transplant Recipient with Autosomal Dominant Polycystic Kidney Disease.

Some experimental studies have suggested a beneficial effect of the mammalian target of rapamycin (mTOR) inhibitor use on hepatic and renal cyst growth in patients with autosomal dominant polycystic kidney disease (ADPKD). However, the results of clinical studies are conflicting and the role of mTOR inhibitors is still uncertain. We report the case of a patient with ADPKD who underwent deceased kidney transplantation because of an end-stage renal disease. The evolution was uneventful with an excellent graft function under cyclosporine (CsA) monotherapy. Some years later, the patient developed a symptomatic hepatomegaly due to growth of cysts. CsA was replaced by sirolimus, an mTOR inhibitor, in order to reduce or control the increase in the cyst and liver volume. Despite the switch, the hepatic volume increased by 25% in two years. Finally sirolimus was stopped because of the lack of effect on hepatic cyst growth and the presence of sirolimus side effects. The interest of our case resides in the followup by MRI imaging during the mTOR inhibitor treatment and 15 months after the restart of the initial immunosuppressive therapy. This observation indicates that mTOR inhibitors did not have significant effect on cyst-associated hepatic growth in our patient, which is consistent with some results of recent large clinical studies.

Population pharmacokinetics of ganciclovir in solid-organ transplant recipients receiving oral valganciclovir.

Valganciclovir (VGC) is an oral prodrug of ganciclovir (GCV) recently introduced for prophylaxis and treatment of cytomegalovirus infection. Optimal concentration exposure for effective and safe VGC therapy would require either reproducible VGC absorption and GCV disposition or dosage adjustment based on therapeutic drug monitoring (TDM). We examined GCV population pharmacokinetics in solid organ transplant recipients receiving oral VGC, including the influence of clinical factors, the magnitude of variability, and its impact on efficacy and tolerability. Nonlinear mixed effect model (NONMEM) analysis was performed on plasma samples from 65 transplant recipients under VGC prophylaxis or treatment. A two-compartment model with first-order absorption appropriately described the data. Systemic clearance was markedly influenced by the glomerular filtration rate (GFR), patient gender, and graft type (clearance/GFR = 1.7 in kidney, 0.9 in heart, and 1.2 in lung and liver recipients) with interpatient and interoccasion variabilities of 26 and 12%, respectively. Body weight and sex influenced central volume of distribution (V(1) = 0.34 liter/kg in males and 0.27 liter/kg in females [20% interpatient variability]). No significant drug interaction was detected. The good prophylactic efficacy and tolerability of VGC precluded the demonstration of any relationship with GCV concentrations. In conclusion, this analysis highlights the importance of thorough adjustment of VGC dosage to renal function and body weight. Considering the good predictability and reproducibility of the GCV profile after treatment with oral VGC, routine TDM does not appear to be clinically indicated in solid-organ transplant recipients. However, GCV plasma measurement may still be helpful in specific clinical situations.

Disposition of valganciclovir during continuous renal replacement therapy in two lung transplant recipients.

OBJECTIVES: To determine whether valganciclovir 450 mg every 48 h for cytomegalovirus (CMV) prophylaxis provides appropriate ganciclovir exposure in solid organ transplant recipients during continuous renal replacement therapy (CRRT). PATIENTS AND METHODS: Ganciclovir pharmacokinetics was intensively studied in two lung transplant recipients under valganciclovir 450 mg every 48 h over one dosing interval. In vitro experiments using blank whole blood spiked with ganciclovir further investigated exchanges between plasma and erythrocytes. RESULTS: Ganciclovir disposition was characterized by apparent total body clearance of 3.3 and 5.8 L/h, terminal half-life of 16.9 and 14.1 h, and apparent volume of distribution of 60.3 and 104.9 L in Patients 1 and 2, respectively. The observed sieving coefficient was 1.05 and 0.96, and the haemofiltration clearance was 3.3 and 3.1 L/h. In vitro experiments confirmed rapid efflux of ganciclovir from red blood cells into plasma, increasing the apparent efficacy of haemofiltration. CONCLUSIONS: A valganciclovir dosage of 450 mg every 48 h appears adequate for patients under CRRT requiring prophylaxis for CMV infection, providing concentration levels in the range reported for 900 mg once daily dosing outside renal failure.

Meningococcal disease in a kidney transplant recipient with mannose-binding lectin deficiency.

We describe the case of a kidney transplant recipient who developed meningococcemia, without meningeal signs, 2 months after transplantation. Plasma levels of complement components C3, C4, and CH 50 were within the normal range. However, using a method to screen for the functional activity of all 3 pathways of complement, no activation via the mannose-binding lectin (MBL) pathway could be detected (0%). A subsequent quantification of MBL pathway components revealed normal levels of MASP 2 but undetectable amounts of MBL. To our knowledge, this is the first report of meningococcal disease after organ transplantation in a patient with MBL deficiency.

[Clinical and genetics aspects of Alport syndrome]. / Aspects cliniques et génétiques du syndrome d'Alport.

Microscopic haematuria of glomerular origin, without known aetiology, should raise the suspicion of Alport Syndrome IASI in children as well as in adults. The genetic mutations causing AS lie in the genes encoding for the alpha3, alpha4 and alpha5 chains of the collagen type IV, the main constituent of glomerular basement membranes (GBM). The various mutations and modes of transmission of the disease account for the heterogeneous clinical presentations. No specific treatment of AS is currently available. However, a better understanding of the GBM's ultrastructure, in particular of type IV collagen, will hopefully enable the identification of novel therapeutic targets.

Sirolimus-induced acneiform eruption.

Sirolimus is a new immunosuppressive agent used to prevent rejection in renal allograft recipients in order to reduce the need of potentially nephrotoxic calcineurin inhibitors (cyclosporine, tacrolimus). The cutaneous side effects of sirolimus are not well known and they may have been underestimated. We report 2 cases of follicular acneiform eruptions induced by sirolimus in renal allograft recipients. This dermatologic complication was severe and difficult to treat, and resolved only after discontinuation of sirolimus.

Treatment of cytomegalovirus infection or disease in solid organ transplant recipients with valganciclovir.

Valganciclovir (VGC) has proved efficacious and safe for the prophylaxis against cytomegalovirus (CMV) in high-risk transplant recipients and for the treatment of CMV retinitis in AIDS patients. We used VGC for the treatment of CMV infection (viremia without symptoms) or disease (CMV syndrome or tissue-invasive disease) in kidney, heart, and lung transplant recipients. Fourteen transplant recipients were treated: five for asymptomatic CMV infection and nine for CMV disease. VGC was administered in doses adjusted to renal function for 4 to 12 weeks (induction and maintenance therapy). Clinically, all nine patients with CMV disease responded to treatment. Microbiologically, treatment with VGC turned blood culture negative for CMV within 2 weeks in all patients and was associated with a > or =2 log decrease in blood CMV DNA within 3 weeks in 8 of 8 tested patients. With a follow-up of 6 months (n = 12 patients), asymptomatic recurrent CMV viremia was noted in five cases, and CMV syndrome noted in one case (all cases in the first 2 months after the end of treatment). VGC was clinically well tolerated in all patients; however, laboratory abnormalities occurred in three cases (mild increase in transaminases, thrombocytopenia, and pancytopenia). This preliminary experience strongly suggests that therapy with VGC is effective against CMV in organ transplant recipients; however, the exact duration of therapy remains to be determined: a longer course may be necessary to prevent early recurrence.

[IgA nephropathy: what you have need to know in 2005]. / Maladie de Berger: que faut-il savoir en 2005?

Although considered as a benign glomerulopathy, IgA nephropathy (IgAN) is now a well-known cause of end-stage renal disease (ESRD). Fifty percent of people suffering from IgAN developp renal insufficiency and 20 to 30% may reach ESRD after 20 to 25 years of evolution. ACEI is indicated to obtain a thigh control of blood pressure and to reduce proteinuria. Corticosteroids alone or in association with immunosuppressants are indicated for agressive, proliferative form of the disease or when there is an unfavorable outcome despite symptomatic treatment.

Dual transplant of marginal kidneys. Case report and review of the literature.

INTRODUCTION: Double transplantation is one possible answer to the shortage of donor organs. While each donor kidney would be unsuitable when considered as a single allograft, use of both kidneys should provide sufficient nephron mass for effective glomerular filtration. CASE REPORT: This is the first Swiss report of a dual adult transplant of marginal kidneys in a 46-year-old man, who was transplanted for the fourth time. Follow-up at 6 months is excellent without acute rejection. CONCLUSION: Recent analysis of dual marginal versus single ideal transplant outcomes, found a comparable 1-yr graft survival in both of the procedures. Long term results are still lacking and guidelines to decide between single, double or no transplantation are emerging.

[Orthostatic proteinuria and compression of the left renal vein (nutcracker syndrome)]. / Protéinurie orthostatique et phénomène de compression de la veine rénale gauche (nutcracker syndrome).

INTRODUCTION: The pathogenic mechanism of orthostatic proteinuria has not yet been clearly established. OBSERVATION: In a tall, thin, 21 year-old man, isolated proteinuria was discovered during an urological control conducted one year after a bilateral orchidopexy following left testicular torsion. Proteinuria was orthostatic. Doppler examination of the kidney revealed an entrapment of the left renal vein (nutcracker phenomenon-NCP). COMMENTS: An NCP was diagnosed in a young patient presenting with orthostatic proteinuria. By provoking modifications in intraglomerular haemodynamics, the NCP may, in nearly half of the cases, be at the origin of orthostatic proteinuria. Doppler examination is the diagnostic method of choice in the screening for NCP.

Idiopathic membranous glomerulonephritis is associated with altered patterns of self-reactive IgM and IgG antibody repertoires.

Idiopathic membranous glomerulonephritis (MGN) is an immune complex nephropathy characterized by the subepithelial deposition of immunoglobulin (Ig)G. The pathogenesis of the disease remains largely unknown, but recent evidence suggests that human MGN may involve an autoimmune component. In the present study, we have analyzed the IgM and IgG antibody repertoires of patients with MGN towards self- and nonself-antigens using a technique of quantitative immunoblotting on a panel of whole human tissue or solubilized bacterial cell extracts as sources of antigens. Data were compared by means of multiparametric statistical analysis. We demonstrate that the antibody repertoires of self-reactive IgM and IgG in plasma of patients with MGN exhibit significantly altered patterns of reactivity, as compared with those of healthy controls. In contrast, multiparametric statistical analysis does not discriminate the reactivity patterns of IgM and IgG in plasma of patients and healthy controls towards nonself antigens. These observations indicate that a failure in the regulation of physiological self-reactivity is associated with immune complex nephropathy in MGN.

[Microscopic polyangiitis]. / La polyangéite microscopique.

Microscopic polyangiitis is a non-granulomatous necrotizing vasculitis involving small vessels. Clinical manifestations are highly polymorphic, but rapidly progressive glomerulonephritis is one of the most frequent and most severe manifestations of the disease. Biopsy of an affected organ and detection of circulating anti-neutrophil cytoplasmic antibodies (ANCA) are key elements for the positive diagnosis of microscopic polyangiitis. Biopsies can disclose necrotizing vasculitis affecting small vessels, without granulomas and without immune deposits. ANCA are very specific for microscopic polyangiitis, Wegener's granulomatosis and Churg-Strauss syndrome when they are positive by indirect immunofluorescence and are directed against myeloperoxidase or proteinase 3. Such ANCA are found in about 70% of patients with microscopic polyangiitis. Treatment of severe forms of microscopic polyangiitis is based on the administration of pulse methylprednisolone, oral corticosteroids and cyclophosphamide. In the mildest forms of the disease, one can probably try either to competely avoid using immunosuppressive drugs, or to replace cyclophosphamide with azathioprine. Treatment induces a complete remission of the disease in more than 90% of cases, but about 30% of the patients will experience a relapse, and progressive worsening of renal function can occur in patients with severe chronic renal failure.