Urinary sediment ICAM-1 level in lupus nephritis.

BACKGROUND: Urinary intercellular adhesion molecule-1 (ICAM-1) level is potentially a valuable biomarker of lupus nephritis (LN), but because ICAM-1 is a cell-surface molecule, soluble ICAM-1 level in urinary supernatant measured by ELISA may not be biologically relevant. METHODS: The ICAM-1 level in urine sediment of 12 LN patients, 10 patients with pauci-immune necrotizing glomerulonephritis (NecGN), and six healthy controls were determined with a polymerase chain reaction (PCR)-based assay. The urinary sediment levels of miR-221, miR-222, miR-339-3P and miR-339-5P, which are involved in the regulation of ICAM-1 production, were also quantified. RESULTS: LN patients had lower urinary sediment ICAM-1 levels than the other two groups (overall p = 0.034). In addition, urinary sediment ICAM-1 level inversely correlated with the estimated glomerular filtration rate (GFR) (r = -0.474, p = 0.026) but not other markers of lupus activity, or urinary sediment levels of miR-221, miR-222, miR-339-3P, or miR-339-5P. However, serum anti-dsDNA level inversely correlated with urinary sediment levels of miR-221 (r = -0.591, p = 0.043) and miR-222 (r = -0.689, p = 0.013), while urinary sediment miR-221 level also correlated with serum C3 level (r = 0.658, p = 0.02). CONCLUSIONS: We conclude that urinary sediment ICAM-1 level was significantly reduced in LN, and the level inversely correlated with renal function. Urinary sediment miR-221 and miR-222 levels correlate with lupus disease activity and may serve as biomarkers of LN.

Fracture risk after thiazide-associated hyponatraemia.

BACKGROUND/AIM: Although thiazide-type diuretics can promote a positive calcium balance, thiazide can be associated with hyponatraemia, which is recently linked with heightened fracture risk. We examine the chance of developing fracture in patients with and without hyponatraemia after taking thiazide diuretics. METHODS: In this single-centre retrospective study, we followed up a previously published cohort of patients with (n= 223) and without (n= 216) thiazide-induced hyponatraemia. RESULTS: A total of 61 osteoporotic fractures was recorded during a mean follow-up period of 82 months. Using univariate regression analysis, the hazard ratio of thiazide-induced hyponatraemia was 1.78 (95% confidence interval (CI), 1.05-3.03; P= 0.033). Cox proportional hazards regression analysis, however, showed that age, body mass index and diabetes mellitus were the only independent predictors of osteoporotic fractures. No association of a history of thiazide-induced hyponatraemia and risk of fracture was evident in the final model. CONCLUSION: Since a history of thiazide-induced hyponatraemia is associated with osteoporotic fracture in univariate but not multivariate analyses, an alternative explanation is that confounding factors of older age and low body mass index accounted for the apparently increased risk of osteoporotic fracture in patients with thiazide-induced hyponatraemia.

Serum and urinary free microRNA level in patients with systemic lupus erythematosus.

MicroRNAs circulating in body fluid have been suggested as biomarkers of various diseases. We studied the serum and urinary level of several miRNA species (miR-200 family, miR-205 and miR-192) in patients with systemic lupus erythematosus (SLE). We studied 40 SLE patients. Serum and urinary miRNA levels were determined and compared with that of healthy controls. The serum levels of miR-200a, miR-200b, miR-200c, miR-429, miR-205 and miR-192, and urinary miR-200a, miR-200c, miR-141, miR-429 and miR-192 of SLE patients were lower than those of controls. Glomerular filtration rate (GFR) correlated with serum miR-200b (r = 0.411, p = 0.008), miR-200c (r = 0.343, p = 0.030), miR-429 (r = 0.347, p = 0.028), miR-205 (r = 0.429, p = 0.006) and miR-192 (r = 0.479, p = 0.002); proteinuria inversely correlated with serum miR-200a (r = -0.375, p = 0.017) and miR-200c (r = -0.347, p = 0.029). SLE disease activity index (SLEDAI) inversely correlated with serum miR-200a (r = -0.376, p = 0.017). Serum miR-200b (r = 0.455, p = 0.003) and miR-192 (r = 0.589, p < 0.001) correlated with platelet count, while serum miR-205 correlated with red cell count (r = 0.432, p = 0.005) and hematocrit (r = 0.370, p = 0.019). These pilot results suggested that miRNA may take part in the pathogenesis of SLE. Further studies are needed to validate the role of serum miRNA as a biomarker of SLE.

Measurements on the routine chest radiograph as prognostic markers in Chinese peritoneal dialysis patients.

BACKGROUND: Fluid overload is a common problem in peritoneal dialysis (PD) patients. Cardiothoracic ratio (CTR) and vascular pedicle width (VPW) in routine chest radiograph are useful indicators of intravascular volume status and may represent important prognostic factors of PD patients. METHODS: We measured VPW and CTR in 286 unselected prevalent PD patients. VPW was further adjusted for the thoracic diameter (VPWR). One-year actuarial survival, technique survival, and duration of hospitalization were analyzed. RESULTS: The mean values of VPW, CTR, VPWR were 47.31 ± 4.73 mm, 0.542 ± 0.074, 0.170 ± 0.024, respectively. VPW correlated with age (r = 0.143; p = 0.016), body weight (r = 0.371; p < 0.001), body height (r = 0.271; p < 0.001), and Charlson's index score (r = 0.153; p = 0.01). One-year patient survival was 87.8%, and technique survival was 82.2%. None of the radiological measurements had an independent effect on one-year actuarial or technique survival by multivariate analysis. Both CTR and VPWR correlated with the duration of hospitalization (r = 0.192 and 0.186, respectively (p = 0.001 and 0.002). Multivariate regression analysis by log-linear modeling showed that independent predictors of one-year hospitalization were VPWR, serum albumin, and SGA overall score. CONCLUSIONS: In Chinese PD patients, VPW was significantly correlated with age, body weight, body height and Charlson's index score. VPWR was an independent predictor of the duration of hospitalization. Further studies are needed to confirm the prognostic value of these radiographic measurements in PD patients.

Relationship between carnosinase gene CNDP1 leucine repeat polymorphism and the clinical outcome of Chinese PD patients.

BACKGROUND: pre-clinical studies showed that carnosine may have a beneficial cardiovascular effect. We studied the effect of tri-nucleotide repeat (CTGs) polymorphisms in exon 2 of the CNDP1 gene, which codes for carnosinase and is responsible for the degradation of carnosine, on the clinical outcome of Chinese peritoneal dialysis (PD) patients. METHODS: we studied 442 PD subjects. Genotyping was done by direct sequencing of genomic DNA. Patients were followed for 43.5 ± 16.2 months. RESULTS: the prevalence of 6-6, 5-6, 5-5 and 4-6 CTGs genotypes was 80.3%, 18.6%, 0.9% and 0.2%, respectively. A total of 270 patients (61.1%) developed the primary composite end point during follow-up. The 5-year event-free survival of the 6-6 CTGs and non 6-6 group was 37.1% and 21.3%, respectively (log rank test, p = 0.3). CONCLUSION: the CTGs polymorphism of the CNDP1 gene does not affect survival of Chinese PD subjects. The role of carnosine and CNDP1 gene polymorphism in the pathogenesis of cardiovascular disease requires further study.

Relation between polymorphisms of receptor for advanced glycation end products (RAGE) and cardiovascular diseases in Chinese patients with diabetic nephropathy.

BACKGROUND: Interaction of receptor for advanced glycation end products (RAGE) with advanced glycation end products (AGEs) is an important pathogenic mechanism of diabetic complications. Three mutations in the promoter region of the RAGE gene (T-429C, T-374A and a 63 bp deletion spanning from -407 to -345 nucleotides) were known to have increased transcriptional activities. We investigated the relationship between these polymorphisms and the risk of cardiovascular diseases in Chinese subjects with overt diabetic nephropathy. METHODS: A total of 219 Type 2 diabetic subjects with nephropathy were recruited. Genotyping of the three polymorphisms in the genomic DNA was done by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Patients were followed for 8 years for the development of cardiovascular events and survival. RESULTS: The T-429 C and T-374 A polymorphism had no effect on the event-free survival of the subjects. For the 63 bp deletion polymorphism, the event-free survival was 37.0% and 63.2% at 96 months for del-/- and del-/+ genotypes, respectively (log-rank test, p = 0.034). After adjusting for confounders, the 63 bp deletion polymorphism had a marginal effect on event-free survival (adjusted hazard ratio: 3.517, 95% CI: 0.852 - 14.521, p = 0.082). Subjects without any mutation of the three polymorphisms have significantly higher risk of first ischemic heart disease than those with any of the three mutations (adjusted hazard ratio: 0.218, 95% CI: 0.062 - 0.764, p = 0.017). CONCLUSION: The 63 bp del-/+ genotype of the RAGE gene has a marginal benefit on the cardiovascular event-free survival in subjects with diabetic nephropathy. Subjects with any of the three mutations have a lower risk of ischemic heart disease. The role of RAGE in the pathogenesis of cardiovascular disease in diabetic patients requires further study.

Tacrolimus for the treatment of systemic lupus erythematosus with pure class V nephritis.

OBJECTIVES: The treatment of pure membranous (class V) lupus nephropathy remains unsatisfactory. We studied the efficacy and safety of tacrolimus in the treatment of membranous nephritis secondary to SLE. METHODS: We recruited 18 consecutive SLE patients (tacrolimus group) with recently confirmed biopsy-proven class V lupus nephritis. They were treated with a tailing dose of oral prednisolone and tacrolimus 0.1-0.2 mg/kg/day for 6 months, followed by maintenance prednisolone and AZA. The rate of resolution of proteinuria and SLEDAI were compared with 19 historical controls treated with oral cyclophosphamide or AZA (control group). All patients were followed for 12 months. RESULTS: Baseline clinical characteristics were comparable between the groups. For the tacrolimus group, the complete and partial remission rates were 27.8 and 50.0%, respectively at 12 weeks; for the control group, they were 15.8 and 47.4%, respectively (overall chi-square test, P = 0.5). However, tacrolimus group had faster resolution of proteinuria than the control group by the general linear model with repeated measures (P = 0.032). At 12 weeks, proteinuria was reduced by 76.2 +/- 17.0% for the tacrolimus group and 47.1 +/- 51.1% for the control group (P = 0.028). Serial change in renal function and SLEDAI score did not differ between the groups. During the study period, four patients of the tacrolimus group, and 11 of the control group, developed lupus flare (P = 0.027). There was no serious adverse effect in the tacrolimus group. CONCLUSIONS: A 6-month course of tacrolimus is a safe and effective treatment of pure class V (membranous) lupus nephritis. As compared with conventional cytotoxic treatment, tacrolimus possibly results in a faster resolution of proteinuria, and a lower risk of lupus flare within 1 yr. The long-term effect and optimal regimen of tacrolimus require further study.

Sevelamer treatment strategy in peritoneal dialysis patients: conventional dose does not make best use of resources.

BACKGROUND: The significant incremental expense in the use of conventional sevelamer dose prompted us to evaluate the role of prescribing a lower dose of sevelamer. METHODS: To determine the optimum strategy for prescribing sevelamer in peritoneal dialysis patients, we conducted an open-label randomized study comparing the treat-to-goal strategy (4.0-g daily sevelamer dose) with lower sevelamer dose (1.2-g daily dose). RESULTS: Twenty-seven peritoneal dialysis patients with serum calcium x phosphorus product above 55 mg2/dL2 were recruited. Eighteen were randomized to the low-dose treatment group (1.2 g daily), and 9 to the treat-to-goal (4.0 g daily) group. Overall, significantly lower calcium x phosphorus product and serum phosphorus levels at 6 months were achieved by the treat-to-goal treatment. The proportions of patients who attained the Kidney Disease Outcomes Quality Initiative (K/DOQI) treatment target, however, did not differ significantly between the treat-to-goal and low-dose treatment groups (66.7% +/- 30.8% vs. 33.3% +/- 21.8%, p=0.10). The numbers needed to treat to benefit 1 patient who attains the K/DOQI recommendation are 1.5 patients (95% confidence interval [95% CI], 1.0-2.8) in the 4.0-g daily dose and 3 patients (95% CI, 1.8-8.7) in the 1.2-g daily dose group. Therefore, an extra 66.7% of subjects would be able to attain the treatment recommendation within the same budget if the daily dose of sevelamer used was 1.2 g instead of the usual 4.0 g. Compared with a 1.2-g daily dose of sevelamer, the 4.0-g daily dose had an incremental cost-effectiveness ratio (ICER) of US $2,353 per additional patient achieving the K/DOQI target. Multivariate analysis showed that only the calcium x phosphorus product after 1 month of sevelamer treatment was predictive of treatment response. CONCLUSIONS: Low-dose sevelamer treatment might be a cost-effective approach, which is "good for many rather than best for a few."

Relation between number of prescribed medication and outcome in peritoneal dialysis patients.

BACKGROUND: Many patients with end-stage renal disease need to take a large number of medications. In the present study, we studied the magnitude of problem and explored the relationship between the number of prescribed medications and the clinical outcome of a large cohort of prevalent peritoneal dialysis (PD) patients. METHODS: We studied the medication list of 266 prevalent PD patients. Dialysis adequacy, residual renal function and nutritional assessment were also performed. The patients were followed for 33.7 +/- 20.7 months. RESULTS: On average, each patient required 4.7 +/- 1.8 type of medications or 10.0 +/- 4.9 tablets per day. 40 patients (15.0%) needed at least 7 types of medication; 33 patients (12.4%) had to take more than 15 tablets each day. There is a significant but weak correlation between the number of types of medication and the Charlson's comorbidity score (r = 0.252, p < 0.001). Despite the large number of medication prescribed, the blood pressure control, serum cholesterol level, and the use of aspirin after atherosclerotic disease remained suboptimal in many patients. By multivariate analysis, independent factors for patient survival were Charlson's comorbidity score, number of types of medication, duration of dialysis, overall SGA score, and mean arterial blood pressure. Each additional type of medication conferred 20% increase in risk of death (95% CI, 1.6-41.7%, p = 0.032), and the effect is independent on the Charlson's comorbidity score. The actual number of pills taken by a patient did not influence survival in this model. CONCLUSION: Our results indicate that the number of prescribed medications is related to the clinical outcome of PD patients. The number of prescribed medication may reflect the severity of uremic complications and comorbid diseases not reflected by the Charlson's comorbidity score. Nevertheless, dialysis physicians should carefully balance the clinical need of treating multiple medical conditions with the potential problems of a complicated therapeutic regimen.

Change in bacterial aetiology of peritoneal dialysis-related peritonitis over 10 years: experience from a centre in South-East Asia.

This study reviewed 1787 episodes of peritoneal dialysis (PD)-related peritonitis in 544 patients between 1994 and 2003. The overall rate of peritonitis was 0.68 episodes/year of PD, but decreased from 1.10 to 0.46 episodes/year between 1994 and 2003. The incidence of peritonitis caused by coagulase-negative staphylococci declined between 1994 and 1998 from 0.21 to 0.06 episodes/year of PD, coinciding with a reduction in the use of spike PD sets. There was a 60.1% response rate to antibiotics throughout the period, but the percentage of cases that required modification of the initial empirical antibiotic regimen rose from 13.6% to 58.7%, indicating that treatment should be individualised.

A case of tuberculosis in a pregnant woman and review of current literature.

Tuberculosis (TB) in pregnancy can present with non-pulmonary symptoms, making diagnosis and treatment challenging. We present a case of TB in a pregnant woman and review current management recommendations.

Influence of climate on the incidence of thiazide-induced hyponatraemia.

The role of hot temperature has been implicated in thiazide-induced hyponatraemia; however, it has never been studied in a systematic manner. The aim of this retrospective study is to correlate the incidence of thiazide-induced hyponatraemia and climate factors in a university teaching hospital from June 1996 to February 2002. We evaluated a representative sample of 201 subjects with thiazide-induced hyponatraemia. Overall, 2.9 +/- 2.2 (range 0-10, median 3) cases of thiazide-induced hyponatraemia were encountered each month during the study period. There was no seasonal variation in the rate of thiazide-induced hyponatraemia (overall chi(2) test, p = 7.0). Thiazide-induced hyponatraemia was not more frequently reported in summer. There was no discernible correlation between the monthly number of cases and average air temperature (r = -0.056, p = 0.65) and relative humidity (r = 0.103, p = 0.40). On the other hand, patients who presented with thiazide-induced hyponatraemia in July and August had significantly higher serum sodium concentration, 118 +/- 7 mmol/l vs. 114 +/- 8 mmol/l in other calendar months (p = 0.016). Temperature showed a statistically significant positive correlation with the level of serum sodium (r = 0.20, p = 0.004). These data demonstrate that there are no seasonal variations in thiazide-induced hyponatraemia disorders, at least in countries with subtropical climate. The question arises whether hypotonic sweat loss mitigates the risk of excessive water drinking in hot summer.

Enterobacteriaceae peritonitis complicating peritoneal dialysis: a review of 210 consecutive cases.

Enterobacteriaceae peritonitis is a serious complication in peritoneal dialysis (PD), but the clinical course of PD-related Enterobacteriaceae peritonitis remains unclear. We reviewed all Enterobacteriaceae peritonitis in our dialysis unit from 1995 to 2004. During this period, there were 1748 episodes of peritonitis recorded; 210 episodes (12.0%) in 123 patients were caused by Enterobacteriaceae. The most common species was Escherichia coli, accounting for 111 episodes. The primary response rate was 84.8% and complete cure rate was 58.1%. The presence of exit site infection was associated with a lower complete cure rate (43.2 versus 61.3%, P = 0.034). A total of 82 episodes (39.0%) did not respond to single antibiotic treatment despite sensitivity in vitro, and a second antibiotic was added. Patients treated with two antibiotics had a marginally lower risk of relapse and recurrence than those with one antibiotic (21.4 versus 36.1%, P = 0.051). The episodes that had recent antibiotic therapy had a marginally lower complete cure rate (49.3 versus 62.8%, P = 0.06). There was a gradual increase in the prevalence of resistance to several commonly used antibiotics over the years. Recent antibiotic therapy was associated with resistance to cefotaxime, ceftazidime, cefoperazone/sulbactam, and piperacillin/tazobactam. We conclude that Enterobacteriaceae peritonitis is a serious complication of PD. Recent antibiotic therapy is the major risk factor of antibiotic resistance. Exit site infection, and probably recent antibiotic therapy, is associated with poor therapeutic response. Contrary to the current recommendation, treatment with two antibiotics may reduce the risk of relapse and recurrence.