K.-M. Chow

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.

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.

Change in bacterial aetiology of peritoneal dialysis-related peritonitis over 10 years: experience from a centre in south-east Asia

ABSTRACT 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.

Urinary mononuclear cell and disease activity of systemic lupus erythematosus.

Mononuclear cells play a cardinal role in the pathogenesis of systemic lupus erythematosus (SLE). A high urine cytology score has been reported to be associated with lupus nephritis in relapse. The objective of this study was to examine the urinary mononuclear cell population of patients with lupus nephritis, and explore its correlation with lupus disease activity. We studied 12 patients with active lupus nephritis, 17 patients with lupus nephritis in remission, 12 SLE patients with no history of renal disease and 13 healthy subjects. Clinical disease activity was quantified by the SLE Disease Activity Index (SLEDAI). Mononuclear cell species in the urinary sediment were examined by immunocytochemistry. Patients with active lupus nephritis had significantly more mononuclear cells in the urinary sediment. The number of + cell was significantly elevated in the active lupus nephritis than the others (P < 0.001), while there was no significant difference in the number of + and + cell among patient groups. The total urinary mononuclear cell correlated significantly with the overall SLEDAI score (r = 0.58, P < 0.001) as well as the renal score (r = 0.57, P < 0.001). The number of urinary +, but not + or +, cell significantly correlated with the overall SLEDAI score (r = 0.46, P = 0.003) as well as the renal score (r = 0.40, p < 0.011). In nine patients with renal biopsy, the histological activity index correlated with the total urinary mononuclear cell (r = 0.75, P = 0.02), + (r = 0.69, P = 0.04) and + cell (r = 0.69, P = 0.04). We conclude that urinary mononuclear cell was markedly elevated in patients with active lupus, and the urinary mononuclear cell count correlated significantly with the SLEDAI score and histological activity. + and + cells are the major component of urinary mononuclear cell in SLE patients and their number correlates with lupus disease activity.

Effect of a compensated Jaffe creatinine method on the estimation of glomerular filtration rate.

Background: Roche Diagnostics has issued new c-fas calibrators for its automated systems. These produce creatinine values that are more comparable with those obtained by high-performance liquid chromatography. However, this results in an underestimation of measured creatinine at concentrations below 155 μmol/L and an overestimation at concentrations above this value. Methods: Serum and urine creatinine concentrations were prospectively determined on samples from 60 patients using the new (compensated) and old (uncompensated) c-fas calibrators, and Passing-Bablok regression analysis was performed. The regression equations thus determined were then used retrospectively to determine the compensated creatinine results (i.e. those results that would have been obtained using the new calibrator) in those serum and urine samples analysed in the previous year using the old uncompensated c-fas calibrator. The compensated creatinine results were then used to estimate the glomerular filtration rate (GFR) by calculating creatinine clearance. This was done by using the formula: UV/Pt, in which U represents the urinary creatinine concentration (μmol/L), V the urinary collection volume (mL), P the serum creatinine concentration (μmol/L) and t the urinary collection time (min). It was also calculated using the abbreviated Modification of Diet in Renal Disease study group (MDRD) formula. Results: The creatinine clearance as determined using either the UV/Pt calculation or the MDRD formula overestimated GFR by ~30% and ~50%, respectively, in normal individuals with a serum creatinine concentration below 155 μmol/L. However, in patients with mild to moderate renal failure (serum creatinine from 155 to 500 μmol/L), changes in creatinine clearances determined by the two procedures were minimal. Conclusion: When laboratories introduce this new, compensated calibrator into practice, it may be appropriate to discuss its potential impact with clinical staff who monitor patients using creatinine clearance.

Extrapolation of reciprocal creatinine plot is not reliable in predicting the onset of dialysis in patients with progressive renal insufficiency

Abstract.  Szeto C.‐C, Leung C.‐B, Wong T.Y.‐H, Chow K.‐M, Wang A.Y.‐M, Lui S.‐F, Li P.K.‐T (Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong Kong, China). Extrapolation of reciprocal creatinine plot is not reliable in predicting the onset of dialysis in patients with progressive renal insufficiency. J Int Med 2003; 253: 335–342.

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.

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 χ2 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.

Public lacks knowledge on chronic kidney disease: telephone survey.

OBJECTIVES To examine knowledge of chronic kidney disease in the general public. DESIGN Cross-sectional telephone survey. SETTING Hong Kong. PARTICIPANTS Community-dwelling adults who spoke Chinese in Hong Kong. RESULTS The response rate was 47.3% (516/1091) out of all subjects who were eligible to participate. The final survey population included 516 adults (55.6% female), of whom over 80% had received a secondary level of education or higher. Close to 20% of the participants self-reported a diagnosis of hypertension. Few (17.8%) realised the asymptomatic nature of chronic kidney disease. Less than half of these individuals identified hypertension (43.8%) or diabetes (44.0%) as risk factors of kidney disease. Awareness of high dietary sodium as a risk factor for chronic kidney disease was high (79.5%). CONCLUSIONS The public in Hong Kong is poorly informed about chronic kidney disease, with major knowledge gaps regarding the influence of hypertension on kidney disease. We are concerned about the publics unawareness of hypertension being a risk factor for kidney disease. Future health education should target areas of knowledge deficits.

Severe bone marrow failure associated with the use of alternating steroid with chlorambucil in lupus membranous nephropathy in Chinese

Severe pancytopenia associated with the use of alternating steroid with chlorambucil regimen was described in six patients with nephrotic syndrome secondary to lupus membranous nephropathy (WHO class V). We believe this is the first report describing the life-threatening degree of marrow toxicity associated with this regimen of alternating steroid with chlorambucil in a Chinese population. Our data suggests that the susceptibility to marrow toxicity with the use of chlorambucil may only be applicable to Chinese patients with underlying systemic lupus erythematosus as a similar degree of toxicity has neither been reported in lupus patients of other ethnic groups nor in non-lupus patients of Chinese origin.