Evaluation of the relationship between cardiac calcification and cardiovascular disease using the echocardiographic calcium score in patients undergoing peritoneal dialysis: a cross-sectional study.

Introduction: An echocardiographic calcium score (ECS) predicts cardiovascular disease (CVD) in the general population. Its utility in peritoneal dialysis (PD) patients is unknown. Methods: This cross-sectional study assessed 125 patients on PD. The ECS (range 0-8) was compared between subjects with CVD and those without. Results: Among the subjects, 54 had CVD and 71 did not. Subjects with CVD were older (69 years vs. 56 years, P < 0.001) and had a higher prevalence of diabetes mellitus (DM) (81.5% vs. 45.1%, P < 0.001). They had lower diastolic blood pressure (72 mmHg vs. 81 mmHg, P < 0.001), lower phosphate (1.6 mmol/L vs. 1.9 mmol/L, P = 0.002), albumin (30 g/L vs. 32 g/L, P = 0.001), parathyroid hormone (34.4 pmol/L vs. 55.8 pmol/L, P = 0.002), total cholesterol (4.5 vs. 4.9, P = 0.047), LDL cholesterol (2.4 mmol/L vs. 2.8 mmol/L, P = 0.019) and HDL cholesterol (0.8 mmol/L vs. 1.1 mmol/L, P = 0.002). The ECS was found to be higher in subjects with CVD than in those without (2 vs. 1, P = 0.001). On multivariate analysis, only DM and age were independently associated with CVD. Conclusion: The ECS was significantly higher in PD patients with CVD than in those without, reflecting a higher vascular calcification burden in the former. It is a potentially useful tool to quantify vascular calcification in PD patients.

An echocardiography-derived calcium score as a predictor of major adverse cardiovascular events in peritoneal dialysis patients-A prospective cohort study.

BACKGROUND: An echocardiography-derived calcium score (ECS) has been shown to predict cardiovascular (CV) mortality in the general population but has not been utilized in the dialysis population. METHODS: We conducted a prospective cohort study including 125 prevalent PD patients. Two blinded and independent echocardiographers determined the ECS for each subject at baseline. The primary outcome was the three-point major adverse cardiovascular events (MACE) which is a composite outcome comprising CV death, non-fatal myocardial infarction and non-fatal stroke. The secondary outcome was all-cause mortality. RESULTS: The mean age was 61 ± 13 years. The median follow-up duration was 40 months (range 1-50). Seventy six (60.8%) of the subjects had diabetes mellitus (DM). The median duration of dialysis was 32 (IQR 16-54) months. The incidences of MACE and all-cause mortality were 13.0 per 100 patient-years and 18.3 per 100 patient-years. Multivariate Cox regression analysis identified the following three independent predictors of MACE: ECS (HR 1.253/unit increase in ECS, 95% CI 1.014-1.547, p = .036), DM (HR 2.467, 95% CI 1.014-6.005, p = .047) and pre-existing cardiovascular disease (CVD) (HR 2.441, 95% CI 1.261-4.728, p = .008); and the following two predictors of all-cause mortality: pre-existing CVD (HR 2.156, 95% CI 1.251-3.714, p = .006) and serum albumin (HR 0.887/g/L increase in serum albumin, 95% CI 0.839-0.937, p < .001). CONCLUSION: The ECS appears to be a significant predictor of MACE in PD patients independently of DM and pre-existing CVD.

Treatment of Severe Tumoral Calcinosis with Teriparatide in a Dialysis Patient after Total Parathyroidectomy.

Tumoral calcinosis is a rare but debilitating condition that can affect dialysis patients. Optimal management is largely unknown. We report the clinical course, treatment, and outcome of a peritoneal dialysis (PD) patient who developed tumoral calcinosis refractory to conventional treatment but improved with teriparatide therapy. A 26-year-old lady on PD for 2 years presented to us with tumoral calcinosis involving bilateral hands. Response to surgical excision, parathyroidectomy, and conversion to hemodialysis failed to result in sustained remission, and tumoral calcinosis progressed. After total parathyroidectomy, the patient had transient but partial remission in which her calcinosis deposits remained but were asymptomatic without pain or clinical signs of inflammation. However, she later experienced a relapse with involvement of the left elbow, right shoulder, right hip, and right thigh. Tumoral calcinosis remained uncontrolled resulting in debilitation, likely attributable to poor calcium and phosphate control because of adynamic bone disease after parathyroidectomy despite treatment of superimposed tuberculosis and therapy with sodium thiosulphate and pamidronic acid. Clinical improvement was however evident after the use of teriparatide. Asymptomatic hypocalcemia occurred after teriparatide therapy but resolved after 2 months. In conclusion, teriparatide appears to be useful for treating tumoral calcinosis in the presence of adynamic bone disease. Hypocalcemia can occur in the initial months of therapy.

Risk factors and clinical course of hungry bone syndrome after total parathyroidectomy in dialysis patients with secondary hyperparathyroidism.

BACKGROUND: Hungry bone syndrome (HBS) is an important postoperative complication after parathyroidectomy for severe secondary hyperparathyroidism (SHPT). There is, however, little data in the literature on its detailed clinical course, and the associated risk factors remain controversial. METHODS: We did a single-center retrospective study on 62 consecutive dialysis patients who underwent total parathyroidectomy for SHPT to examine the risk factors, clinical course and outcome. Data on demographic characteristics, perioperative laboratory parameters including serum calcium, phosphate, alkaline phosphatase (ALP) and parathyroid hormone (PTH), drug treatment for SHPT and operative details of parathyroidectomy were collected. RESULTS: Seventeen (27.4%) patients developed severe postoperative hypocalcemia with HBS. The serum calcium dropped progressively while serum ALP rose after operation until 2 weeks later when serum calcium reached the trough and serum ALP peaked. Serum phosphate also fell but stabilized between 4 and 14 days. The total postoperative calcium and vitamin D supplementation was significantly larger, and hospital stay was significantly longer in the group with HBS as compared with those without HBS. Young age, high body weight, high preoperative ALP level, and low preoperative calcium level independently predicted the development of HBS while preoperative PTH and use of cinacalcet or paricalcitol did not. CONCLUSION: HBS was common after total parathyroidectomy in patients with SHPT, and it is important to closely monitor the postoperative serum calcium, phosphate and ALP levels in the following 2 weeks, especially for those at risk. The implications of our findings on perioperative management are discussed.

Treatment of HCV in renal transplant patients with peginterferon and ribavirin: long-term follow-up.

BACKGROUND: In addition to the observation of an increased viremia among patients with chronic hepatitis C virus (HCV) infection who undergo renal transplantation, fibrosis and necroinflammatory activity have been noted to worsen comparing pre- and post-renal transplantation liver biopsies in some of these patients. Apart from the reported reduced patient and allograft survival rates, post-transplant diabetes mellitus, de novo glomerulonephritis, and an increased overall risk of infection have been observed. However, antiviral therapy for HCV is generally considered contraindicated among patients with solid organ transplants, with the main worry being the risk of acute rejection in relation to the use of interferon. We reported the long-term outcome of four renal transplant patients with chronic HCV infection who received peginterferon-based therapy. METHODS: We collected the long-term follow-up data of four patients who completed the therapy with peginterferon in combination with ribavirin. Two of them had renal impairment at baseline. RESULTS: With treatment, they had a significant improvement in terms of serum liver transaminase level, and two patients achieved the early virological response and the other two rapid virological response. All four patients achieved sustained virological response, with neither HCV flare up nor renal dysfunction during follow-up for a mean duration of 74.3 months after therapy. CONCLUSIONS: These results suggest that sustained HCV virological response may be achieved without allograft dysfunction, in selected renal transplant patients using a peginterferon-based therapy.

Alternating Mupirocin/Gentamicin is Associated with Increased Risk of Fungal Peritonitis as Compared with Gentamicin Alone - Results of a Randomized Open-Label Controlled Trial.

UNLABELLED: ♦ BACKGROUND AND OBJECTIVES: Catheter-related infection, namely exit-site infection (ESI) and peritonitis, is a major infectious complication and remains a main cause of technique failure for patients receiving peritoneal dialysis (PD). Topical application of antibiotic cream might reduce catheter-related infection but emergence of resistant or opportunistic organisms could be a concern. Optimal topical agents and regimens remain to be determined. We did a study to examine the effect of an alternating topical antibiotic regimen in preventing catheter-related infection. ♦ METHOD: We performed a single-center, randomized, open-label study to compare daily topical application of gentamicin cream with a gentamicin/mupirocin alternate regimen to the exit site. Patients randomized to alternating regimen were asked to have daily application of gentamicin cream in odd months and mupirocin cream in even months. Primary outcomes were ESI and peritonitis. Secondary outcomes were catheter removal or death caused by catheter-related infection. A total of 146 patients (71, gentamicin group; 75, alternating regimen group) were enrolled with a total follow-up duration of 174 and 181 patient-years for gentamicin and alternating groups, respectively. All patients were followed up until catheter removal, death, transfer to another unit, transplantation or the end of the study on March 31, 2014. There were no significant differences in the age, sex, dialysis vintage, and rate of diabetes, helper-assisted dialysis and methicillin-resistant Staphylococcus aureus (MRSA) carriage state. ♦ RESULTS: No difference was seen in the time to first ESI or peritonitis. However, the time to first gram-negative peritonitis seemed longer for the gentamicin group (p = 0.055). The 2 groups showed a similar rate of ESI (0.17/yr vs 0.19/yr, p = 0.93) but P. aeruginosa ESI was less common in the gentamicin group (0.06/yr vs 0.11/yr, p < 0.001). There was no difference in the incidence of ESI due to non-tuberculous mycobacteria. Peritonitis rate was significantly lower in the gentamicin group (0.22/yr vs 0.32/yr, p < 0.001), with a striking decrease in gram-negative peritonitis (0.08/yr vs 0.14/yr, p < 0.001), and fungal peritonitis (0.006/yr vs 0.03/yr, p < 0.001), which was all antibiotics-related episodes with antecedent use of systemic antibiotics for the treatment of catheter-related infections. There was no significant difference in the catheter loss or death related to catheter-related infection. ♦ CONCLUSION: Alternating gentamicin/mupirocin cream application appeared as effective as gentamicin alone in preventing ESI except for P. aeruginosa. However, it was inferior to gentamicin in the prevention of peritonitis episodes, especially for those caused by gram-negative organisms. It was also not useful in reducing catheter-related infection due to opportunistic organisms but instead associated with a higher incidence of antibiotic-related fungal peritonitis.

Impact of a low-glucose peritoneal dialysis regimen on fibrosis and inflammation biomarkers.

BACKGROUND: The impact of a low-glucose peritoneal dialysis (PD) regimen on biomarkers of peritoneal inflammation, fibrosis and membrane integrity remains to be investigated. METHODS: In a randomized, prospective study, 80 incident PD patients received either a low-glucose regimen comprising Physioneal (P), Extraneal (E) and Nutrineal (N) (Baxter Healthcare Corporation, Deerfield, IL, USA) (PEN group), or Dianeal (control group) for 12 months, after which both groups continued with Dianeal dialysis for 6 months. Serum and dialysate levels of vascular endothelial growth factor (VEGF), decorin, hepatocyte growth factor (HGF), interleukin-6 (IL-6), macrophage migration inhibitory factor (MIF), hyaluronan (HA), adiponectin, soluble-intracellular adhesion molecule (s-ICAM), vascular cell adhesion molecule-1 (VCAM-1) and P-selectin, and dialysate cancer antigen 125 (CA125), were measured after 12 and 18 months. This paper focuses on results after 12 months, when patients in the PEN group changed to glucose-based PD fluid (PDF). RESULTS: At the end of 12 months, effluent dialysate levels of CA125, decorin, HGF, IL-6, adiponectin and adhesion molecules were significantly higher in the PEN group compared to controls, but all decreased after patients switched to glucose-based PDF. Macrophage migration inhibitory factor level was lower in the PEN group but increased after changing to glucose-based PDF and was similar to controls at 18 months. Serum adiponectin level was higher in the PEN group at 12 months, but was similar in the 2 groups at 18 months. Body weight, residual renal function, ultrafiltration volume and total Kt/V did not differ between both groups. Dialysate-to-plasma creatinine ratio at 4 h was higher in the PEN group at 12 months and remained so after switching to glucose-based PDF. CONCLUSION: Changes in the biomarkers suggest that the PEN PD regimen may be associated with better preservation of peritoneal membrane integrity and reduced systemic vascular endothelial injury.

Screening Algorithm for BK Virus-Associated Nephropathy Using Sequential Testing of Urinary Cytology: A Probabilistic Model Analysis.

BACKGROUND: Incorporating urinary cytology in BK virus (BKV) screening algorithm potentially reduces the screening cost for BK viral nephropathy. We aimed to evaluate the test performances and screening cost of sequential 2-stage screening consisting of urine cytology followed by BKV serum quantitative polymerase chain reaction (PCR). METHODS: Ninety-five kidney transplant recipients who had BKV serum quantitative PCR/urine cytology tested and verified with histopathology (the reference gold standard) were included. A probabilistic model was constructed to evaluate the test performance and screening cost of 2-stage screening, and was compared with screening with urine cytology or serum viral load alone. RESULTS: At a viral load threshold of ≥104 copies/ml, the sensitivity and specificity of quantitative PCR alone were 83% (95% CI 69-96) and 91% (95% CI 83-97), respectively. The sensitivity and specificity of urine cytology alone were 91% (95% CI 79-100) and 74% (95% CI 60-91), respectively. Sequential 2-stage screening resulted in loss in sensitivity but a net gain in specificity (viral load threshold ≥104 copies/ml - sensitivity, 75% (95% CI 60-91); specificity, 98% (95% CI 95-99)). Two-stage screening also had superior positive predictive value and is cost effective when BKV-associated nephropathy prevalence is below 94%. CONCLUSIONS: Our study had demonstrated a favorable test performance and cost efficiency of 2-stage BKV screening.

Persistent sterile peritoneal inflammation after catheter removal for refractory bacterial peritonitis predicts full-blown encapsulating peritoneal sclerosis.

BACKGROUND: Encapsulating peritoneal sclerosis (EPS) is the most serious complication of peritoneal dialysis, having high morbidity and mortality. To improve outcomes, early diagnosis is needed to direct treatment during the early inflammatory phase. However, in the early inflammatory phase, clinical features are nonspecific, and no reliable diagnostic criteria have been established. Because bacterial peritonitis and termination of dialysis are two important risk factors triggering the progression of EPS, patients with refractory bacterial peritonitis necessitating dialysis catheter removal are at particularly high risk of developing EPS. Many of these patients might indeed experience non-resolving sterile peritonitis (probably the inflammatory phase of EPS) before progression to full-blown disease (that is, the presence of intestinal obstruction). We undertook a retrospective study to compare, in this particular situation, the clinical characteristics of patients with or without sterile peritoneal inflammation, assessing their clinical outcomes in terms of short-term mortality and the chance of developing full-blown EPS. METHODS: Our retrospective review included 62 patients whose dialysis catheter was removed because of refractory peritonitis between January 2005 and December 2010. RESULTS: Of the 62 patients identified, 39 (63%) had persistent sterile peritoneal inflammation ("high-risk" group, n = 39), and 23 (37%) had resolution of inflammation without significant intra-abdominal collection after catheter withdrawal ("control" group, n = 23). Compared with the control group, the high-risk group had a significantly longer PD duration (71.6 ± 43.3 months vs 42.3 ± 29.9 months, p = 0.003), a higher dialysate-to-plasma ratio (D/P) of creatinine (0.768 ± 0.141 vs 0.616 ± 0.091, p = 0.004), and a higher computed tomography score for EPS (7.69 ± 2.98 vs 1.00 ± 1.00, p < 0.001). During the 6-month study period, the high-risk group had a higher chance of developing full-blown EPS (31% vs 0%, p = 0.002) and a higher 6-month all-cause mortality (36% vs 4.3%, p = 0.004). CONCLUSIONS: Persistent sterile peritoneal inflammation was common after dialysis catheter removal for refractory bacterial peritonitis, and the patients with such inflammation were at high risk of progression to full-blown EPS.

Atypical mycobacterial exit-site infection and peritonitis in peritoneal dialysis patients on prophylactic exit-site gentamicin cream.

We report 9 cases of exit-site infection and continuous ambulatory peritoneal dialysis peritonitis associated with atypical mycobacteria. All patients had been using topical gentamicin cream as prophylaxis for exit-site infection before the onset of these infections. Gentamicin cream is postulated to be a potential risk factor for atypical mycobacterial infection because of selective pressure on other micro-organisms. The microbiology of atypical mycobacteria and the treatment for atypical mycobacterial infections are discussed.

Kidney allograft failure due to acute phosphate nephropathy associated with severe secondary hyperparathyroidism.

Intratubular calcification is a common finding in renal allografts. However, possible harmful effect of this calcification is not well recognized, and allograft failure purely due to this condition has not been reported. We report a kidney transplant recipient who suffered from severe secondary hyperparathyroidism and unexplained early allograft failure. A diagnosis of acute phosphate nephropathy was made subsequently based on serial allograft biopsy findings. This case calls for a high index of suspicion to look for this rare cause of allograft dysfunction among high-risk patients. It also highlights the importance of good calcium-phosphate control before renal transplantation.

Efficacy of enteric-coated mycophenolate sodium in patients with active lupus nephritis.

BACKGROUND: The ideal treatment of lupus nephritis has yet to be defined. Both cyclophosphamide and mycophenolate mofetil have been used with encouraging results, but adverse events are frequently seen. There are no data on the use of enteric-coated mycophenolate sodium. METHODS: We retrospectively reviewed 12 patients with active forms of lupus nephritis (1 class III, 7 class IV and 4 class V) treated with enteric-coated mycophenolate sodium combined with corticosteroids. RESULTS: The mean age of the patients was 32.3 +/- 11.2 years and the average length of follow up was 25.9 +/- 8.9 months. The mean serum creatinine clearance was 93 +/- 30.1 mL/min per 1.73 m(2) and the mean proteinuria level was 4.5 +/- 3.6 g/day. All had features that warranted aggressive treatment. Mycophenolate sodium was given for 12.9 +/- 9.7 months with an averaged starting dose of 1350 +/- 163 mg/day. Six patients attained complete remission and six attained partial remission with treatment. The mean interval to attain first remission (complete or partial) was 8.3 +/- 5.7 weeks. At last follow up, all patients were in complete or partial remission. Apart from herpes zoster that developed in one patient, no other significant side-effects were encountered. CONCLUSION: Enteric-coated mycophenolate sodium was effective and well-tolerated in the treatment of active lupus nephritis.

Treatment of fungal peritonitis with a combination of intravenous amphotericin B and oral flucytosine, and delayed catheter replacement in continuous ambulatory peritoneal dialysis.

BACKGROUND: Fungal peritonitis (FP) is associated with significant mortality and high risk of peritoneal failure. The optimum treatment for peritoneal dialysis (PD)-associated FP remains unclear. Since January 2000 we have been treating FP with a combination of intravenous amphotericin B and oral flucytosine, together with deferred catheter replacement. We examined the clinical course and outcome of the FP patients treated with this approach (study group). An outcome comparison was also made to an alternatively treated historic cohort (control group). METHODS: This was a single-center retrospective study. The clinical course and outcome of 13 consecutive episodes of FP occurring in 13 patients treated between January 2000 and April 2005 with the study approach were examined. The patients were treated with an incremental dose of intravenous amphotericin B to a target dose of 0.75 - 1 mg/kg body weight/day, and oral flucytosine 1 g/day upon a diagnosis of FP at 3.77 +/- 0.93 days from presentation. Replacement of the peritoneal catheter was intended after complete clearing of effluent, after which, antifungal chemotherapy was continued for another 1 - 2 weeks. Their outcome was compared with 14 historic controls that were treated between April 1995 and December 1999. RESULTS: Mean age of the study group was 58.7 +/- 13.2 years; male-to-female ratio was 2:11; 6 (46.1%) were diabetic. All FP were caused by Candida species (C. albicans, 2; C. parapsilosis, 8; C. glabrata, 3). Two (15.4%) patients died before resolution of the peritonitis. The dialysate effluent cleared in 11 patients (84.6%) after 13.2 +/- 3.3 days of treatment, but 2 patients died of acute myocardial infarction before catheter replacement. Nine patients had their catheters replaced at day 26.7 +/- 7.7 of treatment; all 9 returned to PD after a total of 31 +/- 12.2 days of antifungal chemotherapy. Reversible liver dysfunction was common with this regimen. When compared with the 14 cases in the historic control group (Candida species, 13; Trichosporon, 1), who were treated with amphotericin B, fluconazole, or a combination of the two, and the majority (78.6%) of whose catheters were removed before day 10 of presentation, the study group appeared to have a lower technique failure rate (30.8% vs 78.6%, p = 0.013) and similar all-cause mortality (30.7% vs 28.5%, p = NS), FP-related mortality (15.4% vs 28.5%, p = NS), and length of hospitalization (48.5 +/- 30.2 vs 57.0 +/- 37.7 days, p = NS). However, a significantly earlier commencement of antifungal treatment in the study group (3.8 +/- 0.9 vs 5.8 +/- 2.4 days, p = 0.012) could be an important confounder of outcome. CONCLUSIONS: Combination of intravenous amphotericin B and oral flucytosine with deferred catheter replacement appears to be associated with a relatively low incidence of PD technique failure, without affecting mortality in patients suffering from FP due to yeasts in this preliminary study. Nonetheless, drug-induced hepatic dysfunction was common; close monitoring during treatment is of paramount importance. The reasons accounting for the observed distinctive outcome remain unclear and further study is required to confirm the results and to investigate for the underlying mechanism.

Prevention of fungal peritonitis with nystatin prophylaxis in patients receiving CAPD.

OBJECTIVE: Fungal peritonitis (FP) is a serious complication of continuous ambulatory peritoneal dialysis (CAPD), being associated with significant morbidity and mortality. The role of nystatin prophylaxis during antibiotic therapy in the prevention of FP remains controversial, especially in programs with a modest or low baseline FP rate. The aim of the present study was to evaluate the effect of nystatin prophylaxis on the occurrence of FP in programs with a relatively modest baseline FP rate. PATIENTS AND METHODS: Incident and prevalent patients receiving CAPD between April 1995 and April 2005 at our center were included and divided into 2 groups. The control group included 320 patients (total follow-up 8875 patient-months) being treated without nystatin before October 1999; the nystatin group included 481 patients (total follow-up 13725 patient-months) being treated after October 1999. Nystatin tablets (500,000 units, 4 times per day) were given orally during whatever use of antibiotics to cover the whole course of antibiotic therapy. Occurrence of FP and antibiotic-related FP (AR-FP) in patients with and without nystatin prophylaxis was compared. RESULTS: The two groups were of similar age but the nystatin group had a significantly higher percentage of diabetics. In addition, the nystatin group had a higher proportion of patients using disconnecting twin-bag exchange systems and had a significantly lower peritonitis rate compared with the control. There were 13 and 14 episodes of FP in the nystatin and control groups respectively. The fungal peritonitis rate of the nystatin group was slightly lower than that of the control group (0.011 vs 0.019 per patient-year) but it did not reach statistical significance. There was, however, a significant decrease in the incidence and proportion of AR-FP in the nystatin group compared with the control group, which persisted even after adjustment for the peritonitis rate. Kaplan-Meier analysis further demonstrated significantly better AR-FP-free survival in the nystatin group compared with the control group. No significant side effects were observed for nystatin. Subgroup analyses in patients of the 2 different connecting systems revealed a similar but nonsignificant trend toward reduction of AR-FP in patients given nystatin prophylaxis. CONCLUSION: Oral nystatin prophylaxis might prevent the occurrence of AR-FP in CAPD patients, resulting in a trend toward reduction in the incidence of FP even in programs with a modest baseline FP rate. A large scale, prospective, randomized controlled trial is needed to further examine this issue.

Vibrio vulnificus peritonitis after handling of seafood in a patient receiving CAPD.

Vibrio vulnificus is a marine bacterium and opportunistic human pathogen. Associated infections have contributed to the majority of seafood-related deaths in the United States. In patients with such predisposed clinical conditions as chronic liver disease, immunocompromised state, and end-stage renal disease, this organism has been associated with the development of life-threatening primary septicemia and severe wound infection. However, continuous ambulatory peritonitis dialysis (CAPD)-related peritonitis caused by V vulnificus has not been reported. We describe a patient receiving CAPD who developed peritonitis caused by V vulnificus after handling seafood. This case highlights the importance of strict aseptic technique during CAPD exchanges and calls for an effort in educating our dialysis patients on precautions about seafood handling.

Hepatitis B virus infection in dialysis patients.

Hepatitis B virus (HBV) infection remains a major issue among dialysis patients. It is associated with a high risk of hepatic complication. The liver disease runs a unique clinical course in dialysis patients, as it can progress with modest hepatic inflammation and prominent fibrosis. The conventional cut-off level of serum alanine aminotransferase (ALT) for commencing antiviral therapy may prove too high and inappropriate for dialysis patients, and liver biopsy appears to be the only definitive means to establish the activity of liver disease in dialysis patients. Liver biopsy should be considered in patients with a serum ALT level that is persistently greater than 30 IU/L, or 0.75-fold the upper limit of the normal level, and/or other clinical and laboratory findings that suggest active liver disease. For antiviral treatment, preliminary reports have shown that lamivudine is effective and well tolerated in dialysis patients. However, the long-term efficacy of lamivudine and its optimal effective dose in dialysis patients remain unknown. The prevention of nosocomial transmission among dialysis patients is also important. Universal precaution measures should be strictly observed and the segregation of hepatitis B surface antigen-positive hemodialysis patients should be considered. For HBV non-immune patients, the importance of HBV vaccination should not be overemphasized. Until a new generation of highly immunogenic vaccines that are proven to be safe and effective in patients with end-stage renal disease becomes available, early vaccination before the development of end-stage renal failure remains the best way to secure immunological protection against HBV infection in dialysis patients.

Treatment with cyclophosphamide in elderly-onset nephrotic syndrome.

BACKGROUND: The best treatment of elderly-onset nephrotic syndrome has not been well defined. The use of corticosteroids or combination immunosuppressants may be associated with a significant incidence of side effects in the elderly. There is little data on the use of cyclophosphamide alone. METHODS: We retrospectively reviewed 30 patients with idiopathic elderly-onset nephrotic syndrome treated with cyclophosphamide. RESULTS: Male to female ratio was 2:1, mean age at diagnosis was 72.7 +/- 5.9 years and average length of follow-up was 41.4 +/- 21.3 months. Significant co-morbidities, including hypertension, were present in 57%. A raised serum creatinine level was found in 57%. Biopsy revealed 15 membranous nephropathy, 4 mesangial proliferative Gn, 5 IgA nephropathy, 3 minimal change nephropathy, 2 focal segmental glomerulosclerosis and 1 C1q nephropathy. Cyclophosphamide was given for 32.0 +/- 16.2 weeks with an averaged cumulative dose per patient 177 +/- 84 mg/kg BW. Remission (complete or partial) was attained by 40, 63, 80 and 87% of patients within 12, 24, 36 and 48 weeks of treatment, respectively. Eighteen patients attained complete remission and 9 partial remission after treatment. The mean interval to attain first remission (complete or partial) was 18.9 +/- 14.6 weeks. This was not affected by age (p = NS) or initial albumin level (p = NS). At the time of last follow-up, all but 2 patients were in complete or partial remission with raised serum creatinine levels in 40%. CONCLUSIONS: Cyclophosphamide was effective and well tolerated in the treatment of elderly-onset nephrotic syndrome, with sustained remission and preserved renal function.

Novel mutations of the AGXT gene causing primary hyperoxaluria type 1.

BACKGROUND: Primary hyperoxaluria type 1 (PH1), an inherited cause of nephrolithiasis, is due to a functional defect of the liver-specific peroxisomal enzyme alanine:glyoxylate aminotransferase (AGT). A definitive PH1 diagnosis can be established by analyzing AGT activity in liver tissue or mutation analysis of the AGXT gene. METHODS: The molecular basis of PH1 in three Chinese patients, two with adult-onset and one with childhood-onset recurrent nephrolithiasis, was established by analyzing the entire AGXT gene. RESULTS: Three novel mutations (c2T>C, c817insAG and c844C>T) and two previously reported mutations (c33insC and 679-IVS6+2delAAgt) were identified. c2T>C converts the initiation codon from ATG to ACG, which predicts significant reduction, if not complete abolition, of protein translation. c817insAG leads to a frameshift and changes the amino acid sequence after codon 274. c844C>T changes glutamine at codon 282 to a termination codon, resulting in protein truncation. CONCLUSIONS: This is the first report describing AGXT gene mutations in Chinese patients with PH1. AGXT genotypes cannot fully explain the clinical heterogeneity of PH1, and other factors involved in disease pathogenesis remain to be identified. Our experience emphasizes the importance of excluding PH1 in patients with recurrent nephrolithiasis to avoid delay or inappropriate management.