Adjuvant Low-Dose Cidofovir Therapy for BK Polyomavirus Interstitial Nephritis in Renal Transplant Recipients

BK virus interstitial nephritis (BKVIN) is a serious complication after kidney grafting, necessitating drastic reduction of immunosuppressive therapy in order to enable viral clearance. Despite these measures, progressive graft dysfunction and graft loss occur in the majority of recipients. We diagnosed BKVIN in 21 recipients grafted between 1998 and 2004. Eight of 21 patients were treated with weekly, adjuvant low-dose cidofovir in addition to reduction of immunosuppressive therapy. BKVIN caused irreversible deterioration of graft function in all patients but renal function stabilized after antiviral treatment (creatinine clearance: 51.8-32 mL/min; p=0.001) and no graft loss occurred in cidofovir-treated recipients during 24.8 (8-41) months follow-up. Peak serum cidofovir concentrations were dose-dependent and attained approximately one-tenth of thein vitroEC50 for cidofovir against BK-virus, while pre-treatment with probenecid did not alter peak serum concentrations nor affected the incidence of nephrotoxicity. In fact, no cidofovir-related renal toxicity occurred; few patients had minor transient side effects (nausea, skin rash). In contrast, 9 of 13 patient who received no adjuvant cidofovir therapy lost their graft after median 8 (4-40) months. In this selected group of recipients with BKVIN, the use of adjuvant low-dose cidofovir therapy resulted in prolonged graft survival and stabilized graft function.     

Ask-Upmark Kidney and Tubulointerstitial Nephritis in a Woman with Severe Renal Failure

Abstract

Ask-Upmark kidney is a rare diagnosis of segmental hypoplasia in pediatric population clinically characterized by severe hypertension potentially treatable with partial to total nephrectomy. Although originally was described only as a congenital anomaly, recent data suggest to be caused by vesicoureteral reflux, either in utero or in early childhood and pyelonephritis. The case we reported indicates that Ask-Upmark kidney should be considered as potential cause of hypertension and renal failure both in children and adults. The renal biopsy is necessary for early diagnosis and may consent to normalize blood pressure with nephrectomy; however, if renal damage is severe and progressive with tubulointerstitial nephritis, surgical management is excluded and renal transplant should be considered.     

Nocardia Asteroides Cerebral Abscess in a Renal Transplant Recipient: Short Report

Opportunist central nervous system infections occur in about 5% to 10% of all renal transplant recipients, but reports of brain abscesses are very rare (1). Nocardia asteroides cerebral abscesses are scarce intracranial lesions. They account for only 2% of brain abscesses (2). Published data about these lesions have taken the form of short reports, small case series and reviews. A universally accepted and effective treatment approach has not yet been established. We present a renal transplant patient with a cerebral abscess caused by Nocardia asteroides.     

Repair of Achilles Tendon Rupture Using Autologous Semitendinosus Graft in a Kidney Transplant Recipient

Insertional Achilles tendon injuries can be difficult to treat when minimal tendon tissue remains for anastomosis. Moreover, in the chronic case with tendon shortening, operative repair can be more difficult than acute rupture. It is particularly desirable to reinforce the tendons, in addition to performing primary repair, in patients with renal or systemic diseases because of the accelerated collagen degeneration. Many techniques have been described for the surgical management of Achilles tendon rupture; however, none has shown clear superiority. We report the case of a 50-year-old renal transplant patient with a spontaneous distal Achilles tendon injury that we repaired using the pull-out technique reinforced with an autologous semitendinosus graft. At 2 years postoperatively, the ankle-hindfoot scale score was 92 points, and the postoperative course was without complication. We believe that the free hamstring tendon autograft is advantageous for this repair, because it is easy to handle, has limited donor site morbidity, and preserves the structures around the ankle.     

Heparin-Induced Thrombocytopenia in a Renal Transplant Recipient

Heparin-induced thrombocytopenia (HIT) type II is an immunologically mediated reduction in platelets that increases the risk of arterial or venous thrombosis. It has been reported in up to 5% of patients receiving unfractionated heparin. Unlike other thrombocytopenic coagulopathies, HIT is associated with a high risk of thromboembolic events if not treated with an appropriate anticoagulant alternative. Diagnosis is dependent on assessment of platelet reduction, identification of previous heparin exposure, detection of thrombotic complications and evaluation of laboratory assays. HIT has been well described in surgical patient populations; however, the abdominal organ transplant population is an exception. HIT should be included in the differential diagnosis of patients presenting with thrombocytopenia after transplantation in order to prevent or treat thrombotic complications that can pose a risk to patient or graft survival.     

Course and Relevance of Arteriovenous Fistulas After Renal Transplant Biopsies

Arteriovenous fistulas (AVFs) after renal transplant biopsy are considered harmless. However, verification of the clinical course has not been thoroughly documented. We evaluated the data of our outpatient renal transplant biopsy program regarding the clinical course of AVFs after 2824 biopsies since 2000. We also reviewed all selective renal transplant embolizations. AVFs were the most frequent biopsy complications (8.3%). Seventy-seven percent of AVFs disappeared spontaneously. Renal function in patients with AVFs was not different compared to those without during 2 years of observation. There were no differences in AVFs comparing protocol or indication biopsies, needle size, the time after transplantation, the use of acetylic salicylic acid or serum-creatinine at biopsy. Living or younger donors were less likely to get postbiopsy AVFs. Ten embolizations were performed. Only one patient was from our outpatient biopsy program. Nine others were biopsied as inpatients in the course of complications during 6 weeks after transplant. Six of nine successfully embolized patients profited with improvement of renal function. Large AVFs occur most commonly shortly after transplantation in patients with poor graft function. There is no established test predicting which patient will benefit from embolization; however, Doppler-determined resistive index may help in this regard.     

BK Virus-Specific Antibodies and BKV DNA in Renal Transplant Recipients with BKV Nephritis

We evaluated twenty renal transplant subjects at various stages of BKV nephritis (BKVN) for BKV-specific IgG and IgM antibodies using ELISA technique and BKV-DNA using PCR. They were divided as early onset (n = 7), stabilizing (n = 3), resolved (n = 8) and late onset (n = 2) BKVN. BKV-specific antibodies and BKV-DNA were simultaneously determined. The mean BKV-specific IgG level in early onset and stabilizing BKVN were 64 and 39 EIA units, and were significantly lower than 138 EIA units seen in resolved BKVN, P = 0.007, P = 0.008. The mean BKV-specific IgM levels in stabilizing BKVN was higher than resolved BKVN (130 vs 51 EIA units), P = 0.006. Mean plasma BKV loads for each group were 955,925, 5642 and 42 copies/mL of plasma, respectively. Prospective study in six BKVN cases revealed mean IgG, IgM levels and BKV-DNA at the time of diagnosis of BKVN as 39, 110 EIA units and 586,758 copies/mL of plasma, respectively. After a mean period of 5.2 months, IgG level increased to 120 EIA units (p = 0.0058) and had no detectable viral copies in circulation. Recovery from BKVN and elimination of BKV is associated with the development of BKV-specific IgG antibodies and this provides insight into the role of humoral immunity to BKV in the pathogenesis of BKVN.     

West Nile Virus Encephalitis in a Kidney Transplant Recipient

We describe a case of West Nile virus encephalitis in a 54-year-old kidney transplant recipient. The clinical course was rapid and fatal. Serial CSF samples showed an evolving mononuclear pleiocytosis and serial MRIs showed increasing signs of cytotoxic edema in her basal ganglia. Seroepidemiological testing indicated that the infection was most likely acquired from transfusion of fresh frozen plasma at the time of transplantation.     

The Effect of Pre-existing Ischaemic Heart Disease on Renal Dysfunction in Cardiac Transplant Recipients

Renal dysfunction is a recognized complication of cardiac transplantation and can impact on the life expectancy of an already fragile population. A large proportion of these patients require transplantation because of the consequences of ischaemic heart disease (IHD) which, in turn, is often associated with ischaemic nephropathy. We studied the effect of IHD, diagnosed prior to transplantation, on the renal function of recipients who survived more than 6months after surgery. Of the 168 patients transplanted in a single centre over 15 years, 132 were included in the study. Renal dysfunction was defined as a serum creatinine consistently above 200 micromol/L (2.26 mg/dL). Analysis confirmed that IHD was an independent risk factor for developing renal impairment. In transplant recipients with IHD, closer monitoring is warranted to detect and prevent renal dysfunction or to retard its progression.     

Severe Hepatitis C Infection in a Renal Transplant Recipient Following Hepatitis C Genotype Mismatch Transplant

We report a case of a 32-year-old female with histologically and clinically inactive chronic hepatic C infection, who received a cadaveric renal transplant from a hepatitis C-positive donor with a different genotype. The genotype mismatch (genotype 1 to genotype 2) and change to tacrolimus-based immunosuppression resulted in severe hepatitis C infection characterized by a 10-fold increase in transaminase levels and grade 3 inflammation histologically. Our report highlights the risk of genotype-mismatch transplants in solid organ transplantation.     

Sirolimus-Associated Heavy Proteinuria in a Renal Transplant Recipient: Evidence for a Tubular Mechanism

Sirolimus is a new and potent immunosuppressive agent. Recently, increased proteinuria has been recognized as an important complication. However, the mechanism thereof has remained unclear. We describe a patient who received sirolimus as standard therapy after living donor kidney transplantation. Within 10 days the patient developed a severe proteinuria that disappeared completely after substituting tacrolimus for sirolimus. Renal biopsy disclosed normal glomeruli even without effacement of the podocytic foot processes. Using FITC labeled anti-albumin antibodies we noted complete absence of albumin in the proximal tubules, whereas an abundant albumin staining was observed in a control patient with a comparable level of proteinuria due to a recurrence of focal segmental glomerulosclerosis after transplantation. Our data suggest that sirolimus can induce severe proteinuria, and that reduced tubular protein reabsorption contributes to the protein loss.     

Granulomatous Tubulointerstitial Nephritis in a Kidney Transplant Recipient: Case Report and Review of the Literature

BackgroundGranulomatous tubulointerstitial nephritis (GTIN) is a rare pathologic finding on kidney biopsy. GTIN can be associated with drugs, infection, systemic granulomatous disease, and tubulointerstitial nephritis with uveitis syndrome. We present a case of GTIN in a kidney transplant recipient (KTR) and a literature review of published cases of GTIN in KTRs.Case PresentationA 65-year-old man with a history of pulmonary and ocular tuberculosis (TB), who had undergone deceased donor kidney transplant 8 years prior, was admitted for acute kidney injury, hypercalcemia, and uveitis. His medications included rifabutin, isoniazid, and tacrolimus. Serum laboratory tests revealed creatinine of 2.65 mg/dL (baseline 1.1-1.5 mg/dL) and corrected calcium of 13.2 mg/dL. Hypercalcemia workup showed parathyroid hormone 7 pg/mL, 1,25(OH) vitamin D 54 pg/mL, parathyroid hormone–related peptide <2.0 pmol/L, and angiotensin-converting enzyme 47 U/L. Kidney biopsy showed GTIN with noncaseating granulomas. Universal polymerase chain reaction testing for acid-fast bacilli, fungus, and bacteria was negative. He was treated with prednisone, and his kidney function returned to baseline, and his hypercalcemia resolved.DiscussionGTIN is a rare entity seen in less than 1% of transplanted kidney biopsies. The exactly etiology of this GTIN case remains unknown. TB could not be entirely ruled out, because the patient was receiving active anti-TB therapy. Our literature review showed infection to be the leading cause of GTIN in KTRs and that GTIN with concomitant uveitis remains exceedingly rare. Steroids may be useful in certain cases.