Biomarkers of Tolerance in Kidney Transplantation: Are We Predicting Tolerance or Response to Immunosuppressive Treatment?

We and others have previously described signatures of tolerance in kidney transplantation showing the differential expression of B cell-related genes and the relative expansions of B cell subsets. However, in all of these studies, the index group-namely, the tolerant recipients-were not receiving immunosuppression (IS) treatment, unlike the rest of the comparator groups. We aimed to assess the confounding effect of these regimens and develop a novel IS-independent signature of tolerance. Analyzing gene expression in three independent kidney transplant patient cohorts (232 recipients and 14 tolerant patients), we have established that the expression of the previously reported signature was biased by IS regimens, which also influenced transitional B cells. We have defined and validated a new gene expression signature that is independent of drug effects and also differentiates tolerant patients from healthy controls (cross-validated area under the receiver operating characteristic curve [AUC] = 0.81). In a prospective cohort, we have demonstrated that the new signature remained stable before and after steroid withdrawal. In addition, we report on a validated and highly accurate gene expression signature that can be reliably used to identify patients suitable for IS reduction (approximately 12% of stable patients), irrespective of the IS drugs they are receiving. Only a similar approach will make the conduct of pilot clinical trials for IS minimization safe and hence allow critical improvements in kidney posttransplant management.

Quality of life of living kidney donors: a single-center experience.

Renal transplantation improves the quality of life (QoL) of patients with end-stage renal disease. The preservation of QoL of living kidney donors is paramount. The aim of this study was to assess the QoL pre- and postdonation using Medical Outcome Survey Short Form-36 (SF-36) and to compare with a control group of potential donors who did not proceed with donation. Over a period of 28 years (1978 to 2006), 82 living donor renal transplantations were performed. Of the 78 eligible donors, 66 (85%) participated in the survey. The median postdonation period was 4.6 years (range, 3 months to 27 years). Thirty eight individuals were assessed in the control group. The postdonation SF-36 scores of the donors were not statistically significantly different from those of the control group except in one out of eight dimensions, which was physical role. However, in 44/66 (66%) donors, the postdonation scores were significantly lower compared to their predonation scores because of development of comorbidities such as musculoskeletal pain, migraine, myocardial infarction, diabetes, and peptic ulcers as the time progressed since kidney donation. The age, sex, time since donation, and relationship to recipient did not affect QoL. Eighty three percentage of the donors would have donated again if possible, and 90.9% wished to encourage living kidney donation. We conclude that the QoL of living kidney donors was not different from the healthy controls, although with the passage of time, there was some deterioration of QoL due to development of comorbidities.

De novo membranous nephropathy associated with donor-specific alloantibody.

Recent evidence suggests that alloantibody may play an aetiological role in the pathogenesis of membranous glomerulopathy in native kidneys. There is an increased awareness of the significance of alloantibody on renal transplant outcome, particularly with the development of more sensitive assays. We describe a kidney transplant patient who developed de novo membranous glomerulopathy (DNMG) with heavy proteinuria in the context of a donor-specific alloantibody (DSA) directed against HLA DQ7. Proteinuria resolved and kidney function stabilized following treatment with mycophenolate mofetil and an angiotensin receptor blocker. The titre of the DSA fell in parallel with resolution of the proteinuria. This is the first reported case of DNMG after kidney transplantation clearly associated with a DSA. We hypothesize that de novo membranous glomerulopathy may be an atypical manifestation of acute antibody-mediated damage. Cases of DNMG should be screened for alloantibody and the presence of alloantibody may influence the choice of therapy.

Renal transplantation after endovascular repair of abdominal aortic aneurysm.

An increasing number of abdominal aortic aneurysms (AAA) occur in renal failure patients because of strong association between atherosclerosis and chronic kidney disease. Endovascular aneurysm repair (EVAR) has proven to be an effective modality to treat AAA, particularly in patients with renal disease, because of its several advantages over the standard open procedure, including lower morbidity, shorter operative time, and shorter hospital stay. A Medline search showed a single publication on renal transplantation (RT) following EVAR of AAA. In this context, we report our case of successful RT in a patient who had undergone EVAR 2 years prior for a 5.7-cm AAA. No stent-related complications, such as graft occlusion, dislodgement, dissection, or endoleak, were observed in the perioperative period. The transplanted kidney had primary function leading to a stable serum creatinine of 115 micromol/L at 6 months. Although the long-term outcome of RT after endovascular repair of AAA remains unknown, currently available evidence shows favorable outcomes of EVAR in the normal population, in patients with renal diseases, and in RT recipients; hence, RT should not be denied to renal failure patients who have undergone EVAR in the past.

Vacuum-assisted closure (VAC) therapy in the management of wound infection following renal transplantation.

OBJECTIVES: Wound infection in the setting of immunosuppressed state such as renal transplantation (RT) causes significant morbidity from sepsis, prolongs hospital stay and is expensive. Vacuum-assisted closure (VAC) therapy is a new technique of management of wound based on the principle of application of controlled negative pressure. The aim of this study was to assess the efficacy of VAC therapy in the management of wound infection following RT. MATERIALS AND METHODS: This is a prospective study of a cohort of 180 consecutive RTs performed over a period of 4 years, where the data were retrieved from a prospectively maintained computerised database and case-notes. RESULTS: 9 of 180 (5%) patients developed wound infection following RT which led to cavitations and dehiscence with copious discharge, and refused to heal with conventional treatment. All 9 cases were treated with VAC therapy. The VAC system was removed after a median of 9 (range 3-30) days when discharge from the wound ceased. Four patients were discharged home with portable VAC device and managed on an outpatient basis, where the system was removed after a median 5.5 (range 3-7) days. The median hospital stay after initiation of VAC therapy was significantly shorter (5, range 2-12 days) than on conventional treatment prior to VAC therapy (11, range, 5-20 days) (p=0.003). Complete healing was achieved in all cases. CONCLUSIONS: The use of VAC therapy is an effective and safe adjunct to conventional and established treatment modalities for the management of wound infection and dehiscence following RT. Key words: Renal transplantation, wound infection, vacuum-assisted closure therapy.

Colitis in a renal transplant patient with human herpesvirus-6 infection.

A male patient developed colitis and a thrombotic microangiopathy 3 weeks after renal transplantation. Immunosuppression at the time of presentation was with sirolimus, mycophenolate mofetil, and prednisolone, but without a calcineurin inhibitor. Cytomegalovirus infection was excluded. However, human herpesvirus-6 DNA was detected at high copy number in both blood and colonic epithelium. The patient recovered after reduction in immunosuppression, with nutritional support and ganciclovir therapy.

The advantages of intravenous renal anaemia treatment in an undernourished patient with chronic kidney disease.

The subcutaneous (SC) treatment of renal anaemia in undernourished patients has potential limitations. In this case report we demonstrate the value of intravenous (IV) darbepoetin alfa in such a patient who experienced difficulty tolerating SC recombinant human erythropoietin (rHuEPO) therapy due to severe malnutrition. Intravenous treatment of renal anaemia in a malnourished patient is preferred because the absence of SC fat makes SC administration difficult. In such patients, darbepoetin alfa is the treatment of choice as it is administered less frequently than other erythropoietic therapies and is more effective at maintaining target haemoglobin (Hb) concentrations. In contrast to rHuEPO, darbepoetin alfa also has the additional advantage of bioequivalent IV and SC dose requirements.

Wegener's granulomatosis presenting as acute suppurative interstitial nephritis.

A 78 year old man presented with acute renal failure following a prolonged respiratory illness. A renal biopsy demonstrated severe suppurative interstitial nephritis with normal glomeruli. After nine weeks of antibiotics he remained anuric and a second biopsy demonstrated pauci-immune, necrotising glomerulonephritis. His subsequent clinical course was consistent with a diagnosis of Wegener's granulomatosis and antineutrophil cytoplasmic antibodies (ANCA) were detected. This is the first reported case of Wegener's granulomatosis presenting with an isolated tubulointerstitial lesion.