Urine Monocyte Chemoattractant Protein-1 and Lupus Nephritis Disease Activity: Preliminary Report of a Prospective Longitudinal Study.

Objective. This longitudinal study aimed to determine the urine monocyte chemoattractant protein-1 (uMCP-1) levels in patients with biopsy-proven lupus nephritis (LN) at various stages of renal disease activity and to compare them to current standard markers. Methods. Patients with LN-active or inactive-had their uMCP-1 levels and standard disease activity markers measured at baseline and 2 and 4 months. Urinary parameters, renal function test, serological markers, and renal SLE disease activity index-2K (renal SLEDAI-2K) were analyzed to determine their associations with uMCP-1. Results. A hundred patients completed the study. At each visit, uMCP-1 levels (pg/mg creatinine) were significantly higher in the active group especially with relapses and were significantly associated with proteinuria and renal SLEDAI-2K. Receiver operating characteristic (ROC) curves showed that uMCP-1 was a potential biomarker for LN. Whereas multiple logistic regression analysis showed that only proteinuria and serum albumin and not uMCP-1 were independent predictors of LN activity. Conclusion. uMCP-1 was increased in active LN. Although uMCP-1 was not an independent predictor for LN activity, it could serve as an adjunctive marker when the clinical diagnosis of LN especially early relapse remains uncertain. Larger and longer studies are indicated.

Steroid-induced diabetes mellitus in systemic lupus erythematosus patients: analysis from a Malaysian multi-ethnic lupus cohort.

OBJECTIVE: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease and glucocorticoid is the mainstay of treatment in SLE. The reported incidence of steroid-induced diabetes mellitus (SDM) ranged between 1-53%. We sought to investigate the prevalence and associated factors of SDM in patients with SLE. METHODOLOGY: A total of 100 SLE patients attending the Nephrology/SLE and Rheumatology Clinic, Universiti Kebangsaan Malaysia Medical Centre (UKMMC) who received corticosteroid treatment were recruited. The diagnosis of diabetes mellitus was based on the 2010 American Diabetes Association's criteria. Prevalent cases of SDM were also included. Statistical analysis was performed to determine the factors associated with SDM. RESULTS: Thirteen of them (13%) developed SDM, with the median onset of diagnosis from commencement of glucocorticoid treatment being 8 years (range 0.5-21 years). Although only seven Indians were recruited into the study, three of them (42.9%) had SDM compared to Malays (9.3%) and Chinese (12.8%) (P ≤ 0.05). Univariate and multivariate analysis showed that higher numbers of system or organ involvement in SLE, abdominal obesity, hypertriglyceridemia and daily prednisolone of ≥ 1 mg/kg/day were the important associated factors of SDM (P ≤ 0.05). Meanwhile, hydroxychloroquine (HCQ) use was associated with reduced SDM prevalence (P < 0.05). CONCLUSION: The prevalence of SDM among SLE patients was 13% and Indians were more prone to develop SDM compared to other races. Higher numbers of system involvement, abdominal obesity, hypertriglyceridemia and the use of oral prednisolone of ≥ 1 mg/kg/day were associated with SDM, while HCQ use potentially protects against SDM.

Oral paricalcitol versus oral calcitriol in continuous ambulatory peritoneal dialysis patients with secondary hyperparathyroidism.

BACKGROUND: Secondary hyperparathyroidism (SHPT) is common in end-stage renal disease. Our primary objective was to evaluate the efficacy of oral paricalcitol versus oral calcitriol on serum intact parathyroid hormone (iPTH) and mineral bone parameters in continuous ambulatory peritoneal dialysis (CAPD) patients with SHPT. The secondary objective was to analyze highly sensitive C-reactive protein (hsCRP) and peritoneal membrane function in both groups. METHODS: This was a prospective randomized control trial. CAPD patients with SHPT were randomized to paricalcitol or calcitriol for 15 weeks. Serum intact iPTH, calcium, phosphate and alkaline phosphatase (ALP) were measured at baseline and every 3 weeks. Serum hsCRP and peritoneal membrane functions were measured at baseline and at week 15. RESULTS: A total of 26 patients were enrolled and randomized-12 to paricalcitol and 14 to calcitriol. Serum iPTH reduced significantly in both groups and there was no difference in the incidence of ≥50 % reduction of iPTH between both groups. There was a significant increase in serum calcium in both groups but there were no differences in serum phosphorus across the visits. The incidence of hypercalcemia was the same in both groups. Serum calcium-phosphorus (Ca × P) product increased in the paricalcitol group but decreased in the calcitriol group. Serum ALP decreased significantly in both groups. There were also no differences in pre- and post-treatment serum hsCRP and peritoneal function test (PFT) in both groups. CONCLUSION: Both oral paricalcitol and calcitriol were equally efficacious in reducing serum iPTH but were associated with significantly higher serum calcium. Serum Ca × P product increased in the paricalcitol group and decreased in the calcitriol group. Serum hsCRP level and PFT were not affected by either treatment. A larger randomized controlled trial is indicated to confirm these initial findings.

The role of urinary neutrophil gelatinase-associated lipocalin in lupus nephritis.

BACKGROUND: Urine neutrophil gelatinase-associated lipocalin (uNGAL) has been proposed as a potential biomarker for lupus nephritis (LN) activity. We determined the association between uNGAL with LN activity in systemic lupus erythematosus (SLE) patients compared to the current standard markers of SLE. METHODS: A total of 100 SLE patients with biopsy-proven LN were recruited-47 with active and 53 inactive LN. uNGAL levels were measured. Renal function test, urinary parameters, lupus serology and calculated renal SLE Disease Activity Index-2K (renal SLEDAI-2K) were analyzed to determine their associations with uNGAL. RESULTS: Normalized uNGAL levels (ng/mg creatinine) were significantly higher in patients with active LN compared to those with inactive disease (p=0.01). uNGAL and renal SLEDAI-2K were associated (r=0.32, p=0.001). Multiple logistic regression showed that only serum creatinine and renal SLEDAI-2K were independent predictors of uNGAL levels (p=0.03 and 0.02 respectively). Analysis of the receiver operating characteristic (ROC) curve showed that uNGAL was a potential biomarker for LN. CONCLUSIONS: uNGAL was increased in active LN especially in LN flares. Serial measurements of uNGAL levels may be of value in monitoring response of LN to treatment and for predicting LN flares.

Assessment of fluid status in CAPD patients using the body composition monitor.

AIMS AND OBJECTIVES: To assess the degree of overhydration in our peritoneal dialysis patients and to examine the factors contributing to overhydration. BACKGROUND: Volume control is critical for the success of peritoneal dialysis, but dry weight has been difficult to ascertain accurately. Chronic fluid overload and hypertension are among the leading causes of mortality in dialysis patients. DESIGN: A cross-sectional observational study. METHODS: The body composition monitor (Fresenius Medical Care, Bad Homburg, Germany) is a bioimpedance spectroscopy device that has been validated for the assessment of overhydration. We used this body composition monitor device on all patients on continuous ambulatory peritoneal dialysis at our institution who met the inclusion criteria to assess their degree of overhydration. RESULTS: Thirty four (17 men, 17 women; mean age 44·5 ± 14·2 years) of a 45 continuous ambulatory peritoneal dialysis patients were enrolled. The mean overhydration was 2·4 ± 2·4 l. Fifty per cent of the patients were ≥2 l overhydrated. Overhydration correlated with male gender, low serum albumin, increasing number of antihypertensive agents and duration of dialysis. There was no difference in overhydration between diabetic and non-diabetic patients. Men were more overhydrated than women, had lower Kt/V and were older. Although, there was no difference in blood pressure between the genders, men had a trend towards a higher usage of antihypertensive agents. CONCLUSION: Our study demonstrates that overhydration is common in peritoneal dialysis patients. Blood pressure should ideally be controlled with adherence to dry weight and low salt intake rather than adding antihypertensive agents even in the absence of clinical oedema. RELEVANCE TO CLINICAL PRACTICE: Body composition monitor is a simple, reliable and inexpensive tool that can be routinely used in the outpatient clinic setting or home visit to adjust the dry weight and avoid chronic fluid overload in between nephrologists review.

Assessment of body fluid status in hemodialysis patients using the body composition monitor measurement technique.

AIMS AND OBJECTIVES: The main objective of the study was to correlate the target dry weight in haemodialysis (HD) patients as assessed clinically by nephrologists to those measured by the Body Composition Monitor (BCM - Fresenius) machine. The second objective was to compare pre and postdialysis changes of extracellular fluid and clinical parameters. BACKGROUND: Clinical assessment of target dry weight in HD patients remains problematic. Inaccurate dry weight resulted in hypovolaemic or overhydration states. The BCM (Fresenius) utilises bioimpedance technology for body fluid monitoring and has been extensively validated. DESIGN: This was a prospective cross-sectional study on consecutive patients who underwent HD and gave informed consent. Methods. The target dry weights of these patients were first assessed by their attending nephrologists and appropriate ultrafiltration prescribed. Their body fluid statuses were then measured with the BCM before and after HD treatment. RESULTS: Eighty HD patients (37 men, 43 women) with a mean age of 55 ± 13 years and a mean duration on HD of 71 ± 56 months were studied. The dry weight measured by BCM significantly correlated with dry weight assessed by the nephrologists. The mean dry weight was higher when assessed by the nephrologists compared to that by BCM. Only systolic blood pressure and not other components of blood pressure reduced after HD treatments. CONCLUSION: The BCM is a rapid and easy-to-use tool that can help HD nursing staffs to adjust patients' dry weights between nephrologists' reviews thus optimising HD therapy and patient outcomes. RELEVANCE TO CLINICAL PRACTICE: We propose that experienced HD nursing staff be trained in the use of the BCM or other simple bioimpedance machines to help monitor patient overhydration and approximate dry weight in consultation with the nephrologists responsible for the care of these patients so as to obviate excessive residual overhydration between nephrology reviews.

Systemic lupus erythematosus with a non functioning pituitary macroadenoma.

BACKGROUND: Malignancies are more common in patients with systemic lupus erythematosus (SLE) than the general population. SLE patients are recognized to have higher prolactin levels. However, there are very few reported cases of SLE with pituitary adenomas. CASE REPORT: We report the second case of a pituitary adenoma in a patient with underlying SLE. A 51 year old lady presented with blurred vision and magnetic resonance imaging of the brain demonstrated a pituitary macroadenoma with mildly elevated serum prolactin levels. The diagnosis of a non functioning pituitary macroadenoma was confirmed histologically. The diagnosis of SLE was made on the basis of thrombocytopenia, antinuclear antibodies, anti double stranded DNA antibodies and lupus nephritis (confirmed on renal biopsy). The patient initially received medical therapy with carbegoline, followed by transsphenoidal neurosurgery for the pituitary macroadenoma. SLE with lupus nephritis was treated with steroids and low dose intravenous cyclophosphamide. CONCLUSIONS: Hyperprolactinaemia is prevalent in twenty to thirty percent of SLE patients but it is rarely due to a prolactinoma. The source of excessive circulating prolactin in SLE patients has not been fully determined.

Thickened carotid intima media thickness and carotid atherosclerosis among lupus nephritis patients: the role of traditional and lupus-specific factors.

AIM: The objectives of this study were to investigate the frequency of thickened carotid intima media thickness (CIMT) and atherosclerosis among lupus nephritis (LN) patients and to study their associated risk factors. METHOD: In this cross-sectional study, carotid ultrasonography was performed on consecutive LN patients to determine CIMT and presence of carotid plaques. CIMT was considered to be abnormally thickened if it was more than the 75th percentile matched for age and sex from the 'Carotid Atherosclerosis Progression Study'. The association between thickened CIMT with traditional cardiovascular risk factors and lupus characteristics were examined. A total of 83 patients with the mean age of 33.6 ± 10 years were recruited. RESULTS: Fourteen patients (16.9%) had thickened CIMT and three (3.6%) had carotid plaques. On univariate analysis, traditional risk factors significantly associated with thickened CIMT (P < 0.05) were patient's current age, diabetes mellitus and waist circumference. Meanwhile, a lower serum C4 levels and higher serum C-reactive protein levels were the lupus-specific factors associated with thickened CIMT (P < 0.05, P < 0.05 and P < 0.01, respectively). In logistic regression analysis, the independent predictors of thickened CIMT were age of diagnosis, lower serum C4 levels and waist circumference (P < 0.05). CONCLUSION: More lupus specific factors were independently associated with thickened CIMT, suggesting that a multi-targeted approach of treatment addressing both the lupus and traditional cardiovascular risks are very important. Larger prospective studies of these special risk factors are indicated.

Immunoadsorption and plasmapheresis are equally efficacious as adjunctive therapies for severe lupus nephritis.

This was a prospective randomized controlled trial to evaluate the effects of immunoadsorption (IA) versus conventional PP (PP) as adjunctive therapy in the treatment of severe lupus nephritis (LN). Of 28 patients with biopsy-proven severe LN (ISN/RPS classes III or IV ± V), 14 underwent 36 sessions of PP and the other 41 sessions of IA in addition to our center's standard LN treatment protocol. Three patients in the PP group and 2 in the IA group experienced a transient, marked drop in platelets with the second session. Except for a higher pre treatment mean SLEDAI score in the PP group 17.4 ± 2.0 vs. 13.5 ± 4.8; p = 0.009 and a serum creatinine of 163 ± 7.9 vs. 81.7 ± 10.2; p = 0.33, there were no other baseline differences. Some differences did exist between the two therapies in the immediate post-treatment phase, at 1 and 3 months. Three in IA relapsed, none of PP in third months, whereas two patients relapsed in the PP and none of IA cohorts at 6 months. However, most of these parameters did not differ by 6 months. The pre- and post-therapy SLEDAI scores remained different 12.4 ± 4.5 vs. 9 ± 4; p = 0.04 at 1 month, and at 3 month 13.5 ± 4.7 vs. 7.7 ± 1.1; p = 0.012 but not at 6 months. We conclude that IA and PP were equally well tolerated and efficacious as adjunctive therapy for severe LN.

Glycosaminoglycan treatment in glomerulonephritis? An interesting option to investigate.

Patients with primary and secondary chronic glomerular diseases are at significant risk for progression to end-stage renal disease. Unfortunately the treatment armamentarium is relatively limited in terms both of available agents and of specificity. Experimental evidence supports the idea that heparin-derived agents and glycosaminoglycans (GAGs) favorably affect primary and secondary renal diseases. While a number of clinical exploratory studies have addressed the effect of these agents in microalbuminuric and macroalbuminuric diabetic patients, very few have investigated their activity in nondiabetic renal conditions. This paper will review the experimental and clinical evidence on the use of GAGs in renal disease other than diabetic nephropathy, following the reports of experimental findings supporting their use and the possible mechanisms involved: anticoagulant and antiproliferative activity, effect on growth factors (PDGF, FGF2 and TGF-beta1), inhibition of heparanase, macrophage renal infiltration and of the renin-angiotensin system, and decrease in proteinuria. Targeting these pathogenic loops with GAG treatment might be revealed to be very rewarding from a clinical point of view. Prospective randomized controlled trials with large case populations and definite entry criteria are clearly indicated.

A comparison of calcium, calcitriol, and alendronate in corticosteroid-treated premenopausal patients with systemic lupus erythematosus.

OBJECTIVE: To assess bone mineral density (BMD) changes in patients with systemic lupus erythematosus (SLE) undergoing longterm therapy with corticosteroids (CS) while taking calcium, calcitriol, or alendronate. The primary endpoint was BMD changes at 2 years. METHODS: Premenopausal SLE patients were randomized into 3 groups according to medication: calcium carbonate 500 mg bd (calcium alone), calcitriol 0.25 microg bd plus calcium carbonate 500 mg bd (calcitriol + calcium), and alendronate 70 mg/week plus calcium carbonate 500 mg bd (alendronate + calcium). BMD was measured at baseline and at the end of the first and second years. RESULTS: Ninety-eight patients were recruited. There were 33 patients taking calcium alone, 33 calcitriol + calcium, and 32 alendronate + calcium. On randomization, median duration of CS use was 2.5 years (range 0-20 yrs). Seventy-seven patients (78.6%) completed the study (23 taking calcium alone, 27 calcitriol + calcium, 27 alendronate + calcium). There were no significant differences in mean CS dosages among the 3 groups at the time of BMD measurements. After 2 years, there were no significant changes in BMD in the calcium-alone and calcitriol + calcium groups, apart from a 0.93% (p < 0.001) reduction in total hip BMD in the calcium-alone group. In contrast, the alendronate + calcium group showed significant increases in BMD of 2.69% (p < 0.001) in the lumbar spine and 1.41% (p < 0.001) in total hip. CONCLUSION: Both calcium alone and calcitriol + calcium preserved lumbar spine BMD in premenopausal patients with SLE taking longterm CS at 2 years, whereas alendronate + calcium led to increases in BMD in lumbar spine and total hip. Premenopausal women taking CS should be considered for osteoporosis prophylaxis.