Sydney Cw Tang

QT prolongation and Torsades de Pointes associated with clarithromycin.

Clarithromycin is a macrolide antibiotic that possesses an improved antimicrobial spectrum and side-effect profile compared with erythromycin. Torsades de pointes is known to be related to erythromycin(1–5), but its association with clarithromycin has not been reported. In this article, we describe 2 patients who developed QT prolongation and torsades de pointes after receiving clarithromycin.

Real-time quantitative analysis of polyoma BK viremia and viruria in renal allograft recipients.

Polyoma BK virus (BKV) remains dormant in the urinary tract and circulating leucocytes and becomes reactivated during immunosuppression. BK viruria is prevalent in renal allograft recipients and BK viremia may be related to nephropathy and allograft rejection. How BK viruria and viremia are related in renal allograft patients is undefined. In this study, BKV copies in paired urine and serum samples of renal allograft recipients were measured by a real time quantitative polymerase chain reaction (Q-PCR) to test the hypothesis that their quantitative relationship might help to delineate viral reactivation patterns in these tissues. Urine and plasma samples from 44 renal allograft recipients with stable graft function were collected during outpatient follow-up and the genome copies of BKV were determined by Q-PCR. All patients showed quantifiable viremia and two groups of patients were identified: one group of patients (n=35) showed low viral load (median: 270/ml, range: 108-1000/ml) and the other group (n=9) with high viral load (median: 5x10(4)/ml, range: 2x10(4)-6x10(4)/ml). The corresponding median levels of viruria were 2000 and 900 ml. BK viremia and viruria were not related quantitatively. BK viremia/viruria were also not related to age, immunosuppression, time and source of renal grafts and serum creatinine levels. The absence of a quantitative relationship between BK viremia and viruria may reflect independent BKV reactivation in different tissues during immunosuppression.

Free-hand, ultrasound-guided percutaneous renal biopsy: experience from a single operator

UNLABELLED Percutaneous renal biopsy is a useful diagnostic procedure for many renal diseases. The experience with ultrasound-guided percutaneous renal biopsy from a single operator was reviewed to identify the possible risk factors of complications after the procedure. METHODS AND RESULTS From 1995 to 1998, 203 biopsies (141 on native kidneys with 14G needles, 62 on transplant kidneys with 18G needles) were performed on 186 individuals as clinically indicated. The biopsy tissue specimen was adequate for histological diagnosis in 96.4% of the biopsies performed. IgA nephropathy followed by lupus nephritis were the most frequent diagnoses in our locality. Haematuria was the most common complication observed: mild bleeding occurred in 4.5%, while major complications (those that required blood transfusion or other intervention) were encountered in 1.5% of patients. Impaired renal function was identified as the single most important risk factor of bleeding complication after renal biopsy, while the presence of systemic hypertension or nephrotic syndrome did not increase the risk of bleeding. There was no correlation between bleeding and the type of renal pathology or the number of needle passes. Continuous haematuria may result from blood clot retention in the bladder. Over 97% of the cases were discharged from hospital within 48 h. CONCLUSIONS We conclude that ultrasound-guided renal biopsy remains a safe, fast, and accurate procedure for the definitive investigation of renal diseases.

Tuberculous infection in southern Chinese renal transplant recipients.

Abstract:  A retrospective study of the prevalence and pattern of tuberculosis among renal transplant patients in a single centre in southern China was performed. Twenty‐three cases of tuberculosis were diagnosed among 440 patients between January 1991 and December 2002. There were 18 men and five women. The mean age of the patients was 39.3 ± 13.4 yr. There were 13 living‐related and 10 cadaveric renal transplants. The interval between renal transplantation and the development of tuberculosis ranged from 3 to 127 months with a median of 46 months. There were 18 cases of pulmonary tuberculosis, two cases of pulmonary plus laryngeal tuberculosis, two cases of disseminated tuberculosis, and one case of tuberculosis involving the urinary tract. Diagnosis was established by positive culture for Mycobacterium tuberculosis in 21 patients and response to empirical anti‐tuberculosis treatment in two patients. The duration of symptoms before the diagnosis of tuberculosis was 27 ± 12 d. The patients were treated with standard anti‐tuberculosis drugs for 11 ± 3 months. The anti‐tuberculosis treatment was in general well‐tolerated. Five patients developed transient hepatitis, three patients developed thrombocytopenia and five patients developed gouty arthritis. One patient died 2 months after initiation of anti‐tuberculosis therapy. All other patients completed anti‐tuberculosis treatment. No recurrence of tuberculosis was observed after a median follow‐up of 90 months. We concluded that (i) tuberculosis is prevalent among southern Chinese renal transplant recipients; (ii) high index of suspicion for tuberculosis among renal transplant recipients is warranted to ensure early diagnosis and prompt initiation of treatment; and (iii) treatment with standard anti‐tuberculosis drugs for an extended period of time is well‐tolerated and is associated with favourable outcome.

CLINICAL COURSE AND OUTCOMES OF SINGLE-ORGANISM ENTEROCOCCUS PERITONITIS IN PERITONEAL DIALYSIS PATIENTS

♦ Background and Objectives: Enterococci are part of the normal flora of the gastrointestinal tract. They can cause enteric peritonitis, which is a serious complication of peritoneal dialysis (PD). However, the clinical course and outcome of PD-related Enterococcus peritonitis remains unclear. ♦ Methods: We reviewed all Enterococcus peritonitis episodes occurring in our dialysis unit from 1995 to 2009. ♦ Results: During the study period, 1421 episodes of peritonitis were recorded. Of 29 episodes (2.0%) that were attributable to single-organism Enterococcus, 12 episodes were caused by E. faecalis; 9, by E. faecium; and the remaining 8, by other Enterococcus species. The overall rate of ampicillin resistance was 41.4%. Recent use of antibiotics was associated with the development of ampicillin-resistant Enterococcus (ARE) peritonitis (hazard ratio: 12.53; p = 0.04). The primary response rate of Enterococcus peritonitis was significantly higher than that of Escherichia coli peritonitis (89.7% vs. 69.9%, p = 0.038), but the primary response rate was not significantly lower for ARE peritonitis than for ampicillin-susceptible Enterococcus (ASE) peritonitis (83.3% vs. 94.1%, p = 0.553). However, significantly more patients with ARE had received vancomycin (83.3% vs. 23.5%, p = 0.003), with a longer mean duration of vancomycin treatment (11.8 ± 6.9 days vs. 3.7 ± 6.8 days, p = 0.005). ♦ Conclusions: Recent use of antibiotics was a risk factor for the development of ARE peritonitis. Outcomes in ASE and ARE peritonitis were similar, but vancomycin was required during treatment for ARE peritonitis, in turn possibly predisposing the patients to infections caused by vancomycin-resistant organisms.

LONG-TERM RENAL ALLOGRAFT RECIPIENTS FROM SOUTH-EAST ASIA IN THE PRE-CYCLOSPORIN ERA

The clinical outcome of long-term renal allograft recipients in the Chinese population has not been reported previously. We analysed patients from the pre-cyclosporin era who had grafts that functioned for > 10 years. Forty-five patients (31 men, 14 women; mean age 30, follow-up duration 13.3 years), representing a 10-year graft survival of 53%, were included. Thirty-six patients (80%) received living-related allografts and 9 (20%) received cadaveric or living-unrelated renal transplantation. The mean serum creatinine at last follow-up was 1.36 mg/dl (range, 0.83–4.08). Major posttransplantation complications included: hypertension in 25 (56%), infection in 16 (36%), acute rejection in 15 (33%), lipid disorder in 13 (29%), liver disease in 7 (16%), osteonecrosis in 5 (11%), malignancy in 4 (9%), coronary artery disease in 3 (7%), and diabetes mellitus in 3 (7%). Five grafts were lost: 3 to chronic rejection, and 2 to patients with stable function who died of non-renal causes. Proteinuria correlated strongly with graft function and survival, and marginally with hypertension. In hepatitis B carriers, serum α-feto protein is useful in the early detection of hepatocellular carcinoma. We conclude that while patients in the pre-cyclosporin era can survive with excellent graft function beyond the first decade, the risk of complications leading to significant morbidity still remains even when patients are receiving minimal doses of immunosuppression in the second decade.

An Unusual Organism for PD-Related Peritonitis: Hafnia Alvei

1. Kubota M, Kanazawa M, Takahashi Y, Io H, Ishiguro N, Tomino Y. Implantation of presternal catheter using Moncrief technique: aiming for fewer catheter-related complications. Perit Dial Int 2001; 21(Suppl 3):S205–8. 2. Danielsson A, Blohme L, Tranaeus A, Hylander B. A prospective randomized study of the effect of a subcutaneously “buried” peritoneal dialysis catheter technique versus standard technique on the incidence of peritonitis and exit-site infection. Perit Dial Int 2002; 22:211–19. 3. Kubota M, Ishiguro N, Tomino Y, Koide H. Campylobacter fetus subspecies fetus peritonitis in continuous ambulatory peritoneal dialysis. Nephron 1993; 65:487–8. doi: 10.3747/pdi.2009.00078

CKD prevention: Perspectives in Hong Kong: CKD prevention

Hong Kong experiences a progressive rise in the prevalence of treated end‐stage renal disease (ESRD) as recorded by the Hong Kong Renal Registry managed by the Hospital Authority (HA) that takes care of 90 – 95% of the ESRD burden. The CKD burden is envisaged to be high, as reflected by 2 initiatives – SHARE which detected a high prevalence of urine or blood pressure abnormalities among 1,201 asymptomatic individuals who underwent screening, and RISKS that aimed to further characterize the spread of CKD in the asymptomatic population.

Pyrexia of unknown origin and proteinuria: an enigma solved by renal biopsy.

Mothers taking cyclosporine are often advised against lactation because of significant concentrations in breast milk. A small number of published reports describe undetectable serum cyclosporine levels in infants being breast-fed, concluding that breast-feeding while taking cyclosporine may be safe for infants. Two further cases where the serum cyclosporine level was undetectable in breast-fed infants are described. A 36 years old primigravida had undergone renal transplantation 5 years earlier because of chronic glomerulonephritis. Her medications preconception and throughout pregnancy were cyclosporine 200 mg per day, azathioprine, prednisone, diltiazem and folate Serum creatinine was 74 mmol/L. The pregnancy was uncomplicated, delivering a live female baby weighing 3290 g at 40 weeks gestation. The mother elected to breast-feed exclusively. One week postpartum, when the mothers’ serum cyclosporine was 68 mg/L, the infants serum cyclosporine level was undetectable (lower limit of assay 15 mg/L). The mother continued to breast-feed for 5 months, her infant healthy and renal function was normal. A 27 years old gravida three para one had been diagnosed with lupus nephritis 2 years earlier. Preconception and throughout the pregnancy the woman was treated with cyclosporine 125 mg per day, methyldopa, prednisone and calcitriol. Serum creatinine was 155 mmol/L. The pregnancy was uneventful until 38 weeks gestation when the mother was induced because of deterioration in maternal blood pressure and renal function. A live female baby weighing 3580 g was delivered. The mother elected to breast-feed exclusively, her daughters serum cyclosporine level being undetectable 2 weeks after birth when the maternal serum cyclosporine level was 39 mg/L. The mother continued to breast-feed for 14 months, her daughter thriving with normal renal function. Serum levels have previously been described previously in 14 infants being breast-fed by mothers taking cyclosporine. With one exception the infants’ blood cyclosporine levels were below the detection limit of the assay used. Corresponding maternal serum cyclosporine levels ranged from 55 to 260 mg/L. One infant who demonstrated detectable blood concentrations of cyclosporine did so in spite of surprisingly low concentrations of the drug in the mothers’ milk. There was no adverse effect on infants after exposure to cyclosporine in breast milk for up to 14 months, including no effect on renal function. Prednisolone is safe for breast-feeding and two recent papers concluded that breast-feeding should not be withheld in infants of mothers receiving azathioprine as this does not appear to pose a significant immediate clinical risk. Two studies demonstrated that infants ingested only 0.06–0.5% of the weight-adjusted maternal dose of tacrolimus concluding that maternal tacrolimus therapy may be compatible with breast-feeding. As mycophenolate is transferred to breast milk it is recommended that mothers taking this immunosuppressive do not breast-feed. In conclusion, serum cyclosporine levels were undetectable in two infants breast-fed while their mothers were taking this medication, consistent with the previously published evidence that breast-feeding while taking cyclosporine may be safe. Very limited evidence also suggests breastfeeding may be safe in mothers taking azathioprine and tacrolimus. Further data including long-term safety outcomes are desirable to enable mothers to make informed decisions regarding the safety of breast-feeding while taking immunosuppressive medication. The two mothers described provided written informed consent for they and their infants’ case histories to be published.

Gas in the renal shadow of a plain abdominal X-ray: emphysematous pyelonephritis.

(Fig. 1, lower panel). The most recent measured creatinine clearance was 63 mL/min. The patient had a radical nephrectomy (cytoreductive surgery) followed by the introduction of sorafenib and the immunosuppressive regimen was adjusted. Even though the surgical resected margin was positive for malignancy, the outcome after 28 months of treatment was excellent. There was disappearance of the scattered lesions and regression of the large lung nodule on repeated chest X-ray and CT of the chest. Survival with metastatic RCC would have been only 4 months, if a full resection of all metastatic sites was not achieved. Recently, a p.o. administrated tyrosine kinase inhibitor, sunitinib, was able to prolong the median progression-free survival in metastatic RCC to only 11 months. However, multidisciplinary treatment including sorafenib was shown to stabilize bone metastases of RCC in a renal transplant recipient. We have shown that a combination of everolimus and sorafenib has resulted in prolongation of progression-free survival of metastatic RCC to at least 28 months and supported the rationale that the addition of mTOR inhibitor to tyrosine kinase inhibitor might potentiate the anti-tumoral effects. Not only progression-free survival is extended to at least 28 months but also there is regression of lung metastases. A good quality of life and good renal allograft function are also achieved. Given the incidences of malignancy increased markedly after transplantation, mTOR inhibitor should be considered in long-term maintenance immunosuppression. In conclusion, this is the first case report of regression of lung metastases of advanced native RCC in a renal transplant recipient with the longest progression-free survival after having been treated with sorafenib combined with immunosuppressive regimen consisting of high-level everolimus. The authors thank Professor Vasant Sumethkul for help in revision of the manuscript.