N. C T Kong

The Classification of Glomerulonephritis in Systemic Lupus Erythematosus Revisited

The currently used classification reflects our understanding of the pathogenesis of the various forms of lupus nephritis, but clinicopathologic studies have revealed the need for improved categorization and terminology. Based on the 1982 classification published under the auspices of the World Health Organization (WHO) and subsequent clinicopathologic data, we propose that class I and II be used for purely mesangial involvement (I, mesangial immune deposits without mesangial hypercellularity; II, mesangial immune deposits with mesangial hypercellularity); class III for focal glomerulonephritis (involving <50% of total number of glomeruli) with subdivisions for active and sclerotic lesions; class IV for diffuse glomerulonephritis (involving > or =50% of total number of glomeruli) either with segmental (class IV-S) or global (class IV-G) involvement, and also with subdivisions for active and sclerotic lesions; class V for membranous lupus nephritis; and class VI for advanced sclerosing lesions. Combinations of membranous and proliferative glomerulonephritis (i.e., class III and V or class IV and V) should be reported individually in the diagnostic line. The diagnosis should also include entries for any concomitant vascular or tubulointerstitial lesions. One of the main advantages of the current revised classification is that it provides a clear and unequivocal description of the various lesions and classes of lupus nephritis, allowing a better standardization and lending a basis for further clinicopathologic studies. We hope that this revision, which evolved under the auspices of the International Society of Nephrology and the Renal Pathology Society, will contribute to further advancement of the WHO classification.

Brain calcification in patients with cerebral lupus

Cerebral lupus (CL) is a common cause of morbidity and mortality in patients with SLE. The brain CTs of 27 consecutive adult patients with SLE and various neurological presen tations were reviewed. The median age and duration of neurological symptoms at the time of the brain CT were 30 years (range = 14-51 years) and six days (range = 1 day-22 years), respectively. Eleven patients (41%) had normal CTs. The abnormalities in the remaining patients could be divided into six categories: (a) cerebral atrophy alone (two patients); (b) calcification alone (three patients); (c) infarct(s) alone (five patients); (d) cerebral atrophy and calcification (three patients); (e) cerebral atrophy and infarct(s) (one patient) and (f) cerebral atrophy, calcification and infarct(s) (two patients). Altogether eight patients (30%) (age range = 17-47 years) had intracerebral calcification : the globus pallidus was involved in all, putamen in two, head of the caudate nucleus in one, thalamus in one, centrum semiovale in two and cerebellum in three patients. Two patients had extensive calcifications of most of the basal ganglia, centrum semiovale and cerebellum. There was no relationship between the presence/degree of calcification and age of patients/duration or type of neurological presentation. The pathogenesis of cerebral calcification in CL is unknown. Cerebral lupus must now be included in the differential diagnosis of intracerebral calcification.

Djenkol bean poisoning (Djenkolism): An unusual cause of acute renal failure

This report describes a patient with acute renal failure that resulted from the ingestion of djenkol beans. Features of acute djenkolism include nausea, vomiting, bilateral loin pain, gross hematuria, and oliguria. The blood urea level was 16.2 mmol/L and the serum creatinine was 460 mumol/L. Phase contrast microscopy of the urinary sediment indicated that the hematuria was nonglomerular. Ultrasound of the kidneys showed slightly enlarged kidneys with no features of obstruction. Renal biopsy showed acute tubular necrosis similar to the single animal study reported in the literature. With conservative therapy, which included rehydration with normal saline and alkalinization of the urine with sodium bicarbonate, the acute renal failure resolved. Based on its chemistry, djenkol bean-associated acute renal failure may be analogous to acute uric acid nephropathy.

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 μg 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.

Posterior reversible encephalopathy syndrome in systemic lupus erythematosus: Pooled analysis of the literature reviews and report of six new cases

Introduction Posterior reversible encephalopathy syndrome (PRES) is a rare neurological disorder which is increasingly recognized to occur in systemic lupus erythematosus (SLE). Objective The purpose of this study was to identify the characteristics of SLE patients with PRES and the associated factors of the poor outcome among them. Methods We investigated SLE patients who developed PRES between 2005–2011 at the Universiti Kebangsaan Malaysia Medical Centre. A comprehensive literature search was done to find all published cases of PRES in SLE. Pooled analysis was conducted to identify the factors associated with poor outcome. Results There were 103 cases of PRES in SLE published in the literature but only 87 cases were included in the analysis in view of incomplete individual data in the remaining cases. The majority of the cases were Asians (74.2%), female (95.4%) with mean age of 26.3 ± 8.8 years. PRES was highly associated with active disease (97.5%), hypertension (91.7%) and renal involvement (85.1%). We found that 79 patients had a full recovery (90.8%) with a mean onset of full clinical recovery in 5.6 ± 4.1 days. On univariate analysis and logistic regression analysis the predictors of poor outcome, defined as incomplete clinical recovery or death, were intracranial hemorrhage, odds ratio (OR) 14 (1.1–187.2), p = 0.04 and brainstem involvement in PRES, OR 10.9 (1.3–90.6), p = 0.003. Conclusion Intracranial hemorrhage and brainstem involvement were the two important predictors of poor outcome of PRES. Larger prospective studies are needed to further delineate the risk of poor outcome among them.

Neutrophil Gelatinase-Associated Lipocalin as an Early Marker of Contrast-Induced Nephropathy After Coronary Angiography

We investigated whether serum neutrophil gelatinase-associated lipocalin (NGAL) was an early predictive biomarker of contrast-induced nephropathy (CIN) in patients with chronic kidney disease (n = 100) undergoing coronary catheterization. Serum creatinine (SCr) levels were measured at baseline, 24 hours, and 48 hours post procedure. Serum NGAL was measured preprocedure, 4 hours, and 24 hours post procedure. The frequency of CIN was 11%. In patients with CIN, SCr achieved significance only at 48 hours (P = .006), whereas serum NGAL increased ≥25% from baseline at 24 hours in 7 of 11 patients with CIN (P = .04) but did not change in the other 4. However, serum NGAL also rose ≥25% in 12 of 89 non-CIN patients. This subgroup could have had “incipient CIN.” Serum NGAL delta value at baseline, 24 hours was superior to SCr for early diagnosis of CIN. In conclusion, serum NGAL is an early predictive biomarker for CIN.

Serum neutrophil gelatinase-associated lipocalin and cystatin C are early biomarkers of contrast-induced nephropathy after coronary angiography in patients with chronic kidney disease

We had previously reported on serum neutrophil gelatinase-associated lipocalin (NGAL) as an earlier biomarker of contrast-induced nephropathy (CIN) than serum creatinine (SCr) in 100 patients with chronic kidney disease undergoing coronary angiography.1 We then compared serum NGAL to serum cystatin C (CysC) in the same group of patients. The SCr, estimated glomerular filtration rate, serum NGAL, and serum CysC were measured at baseline and various time points as appropriate postprocedure. The frequency of CIN was 11% (n = 11). Serum NGAL increased ≥25% from baseline at 24 hours in 7 patients with CIN (P = .04). Serum CysC increased ≥25% from baseline at 24 hours in 4 patients with CIN (P = .008). Changes in serum NGAL and serum CysC from baseline at 24 hours (▵ values) could diagnose CIN 24 hours earlier than SCr with serum NGAL showing a superior performance.

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 centers 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.

Gentamicin ototoxicity in continuous ambulatory peritoneal dialysis

A prospective study was undertaken of 10 chronic renal failure patients on Continuous Ambulatory Peritoneal Dialysis (CAPD) complicated by repeated bouts of peritonitis treated with gentamicin. Each 10-day treatment course consisted of a 120 mg loading dose, followed by 16 mg in 21 of peritoneal dialysate, given four times a day. Serum gentamicin analysed by enzyme immunoassay showed a mean level of 5.2 micrograms/ml, (range 3.7 to 6.6 mg/ml) four hours after the loading dose. Similar levels, well within the therapeutic range, were maintained on the 3rd, 5th, 7th and 9th days of intraperitoneal gentamicin therapy, suggesting no accumulation of gentamicin in the serum. Pure tone audiometry, electronystagmography and clinical assessment were performed during each course of treatment. Although no evidence of ototoxicity was found during the first two courses of gentamicin, but disequilibrium and bobbing oscillopsia were present during the third and fourth courses of gentamicin. These findings could be explained by cumulative injury to the vestibular apparatus caused by repeated therapeutic insults.

Influences on bone mineral density in Malaysian premenopausal systemic lupus erythematosus patients on corticosteroids

The aim of this study was to assess the bone mineral density (BMD) of premenopausal patients with systemic lupus erythematosus (SLE) on corticosteroids (CS) and to determine the influence of CS and other risk factors on BMD. A total of 98 premenopausal patients with SLE were recruited from outpatient clinics in two teaching hospitals. Risk factors for osteoporosis were determined, and BMD was measured using dual-energy x-ray absorptiometry. The mean age of the patients was 30.05 ± 7.54 years. The mean dose of prednisolone at time of BMD measurement was 18.38 ± 10.85 mg daily. Median duration of CS use was 2.5 years (range 0–20). Median cumulative dose of CS was 9.04 g (range 0.28–890.0). Six patients (6.1%) had osteoporosis, 41 (41.9%) had osteopenia and 51 (52.0%) had normal BMD. Lumbar spine T score correlated with cumulative CS dose (P = 0.019). Duration of CS intake correlated with femoral neck T score (P = 0.04) and trochanter T score (P = 0.008). There was no correlation between BMD and race, SLE Disease Activity Index score, smoking and self-reported calcium intake or exercise. Only 52% of these patients had normal BMD. The duration and cumulative dose of CS intake was significantly correlated to BMD, but not the other commonly assessed risk factors. These findings suggest that premenopausal patients with SLE on CS should have their BMD measured at regular intervals to fully assess their osteoporosis risk.