Maximum tolerable dose of cyclophosphamide and azathioprine in Pakistani patients with primary renal disease

Objective: The immunosuppressive regimens, at present, mainly rely on western guidelines that were derived from studies conducted in western populations. No such study exists for South Asian population, which is home to almost two billion people different in both genetics and environment from west. Locally derived thresholds for side effects markedly different from western figures may warrant re-adjustment of current local immunosuppressive regimens that are at present based largely on western guidelines. In order to define optimum dose for Cyclophosphamide [CYC] and Azathioprine [AZA] based immunosuppressive therapy, we conducted this study to find out maximum tolerable doses of azathioprine [AZA] and cyclophosphamide [CYC] beyond which neutropenia and thrombocytepenia are most likely to occur in patients with primary renal pathology

Method: Patients with systemic vasculitis and idiopathic glomerulonephritis who were on CYC and AZA were identified through review of medical records at a tertiary care hospital in Pakistan [The Aga Khan University Hospital, Karachi]. Patients were categorized under three principal diagnosis i.e. systemic lupus erythematosus [SLE], primary [idiopathic] glomerulonephritis [GN] and Wegener's granulomatosis [WG]. The Receiver Operating Curve [ROC] was used to calculate the maximum tolerable dose for both CYC and AZA

Results: We identified 94 patients aged 6-82 years [median 44.5 years] with primary renal disease [Wegener's granulomatosis n=13, Systemic lupus erythematosis n=62 and idiopathic glomerulonephritis n=19] who received CYC or AZA. Of these 94 patients, 36.2% [n=34] received CYC and 63.8% [n=60] received AZA. The mean dose of CYC was 1.54 +/- 0.50 mg/kg of body weight [range: 0.77-2.93]. The mean dose of AZA was 1.64 +/- 0.59 mg/kg of body weight [range: 0.47-2.97]. The maximum tolerable doses calculated for CYC and AZA were 1.25 mg/kg and 1.30 mg/kg of body weight respectively. The maximum tolerable dose for CYC and AZA among males could not be calculated, because of insufficient number of patients who developed neutropenia and thrombocytopenia. The maximum tolerable doses for CYC and AZA among females were 1.34 mg/kg and 1.03 mg/kg of body weight respectively. Also we found out that AZA was relatively more likely to cause neutropenia and thrombocytopenia [p = 0.07]

Conclusion: We thereby recommend that CYC should be initiated at a dose no more than 1 mg/kg of body weight and AZA at an initial dose of 0.75-1.0 mg/kg of body weight. The dose may be adjusted later on the basis of clinical response and laboratory reports

Radiocontrast nephropathy: is it dose related or not?

To assess the safety of high dose non-ionic contrast media during a single radiological procedure in patients with pre-existing renal impairment. One hundred eighteen patients, with serum Creatinine greater than 1.3 mg/dl who were undergoing coronary angiography or percutaneous transluminal coronary angiography [PTCA] were included in the study. All patients received the nonionic dye ULTRAVIST [Iopromide]. Serum creatinine were measured before, 48 hours and 1 week after the administration of contrast agent. An acute contrast induced reduction in renal function was defined as an increase in Serum Creatinine concentration of >=0.5mg/dl, 48 hours after the administration of contrast agent. All patients with end stage renal disease or patients undergoing coronary bypass surgery within a week after coronary angiography or had any concomitant factors that could cause acute renal failure e.g., sepsis, hypotention, etc., were excluded. Patients receiving a dose of upto100 ml of contrast agent [low dose group] were separated from those who received greater than 100 ml of contrast agent [high dose group]. Patients in both groups had similar characteristics in terms of sex, age, weight and underlying disease. Student's t-test was used for statistical analysis. The mean age of our patients was 62.3 + 8.83 [range 40 - 84 years]. There were 93 [78.8%] males and 25 [21.2%] females. The mean pre-contrast creatinine in the low contrast group was 1.97+0.92 and high dose group was 2.16+1.90 [p=0.48]. The post-contrast Creatinine at 48 hours was 2.11+1.11 and 2.06+1.39 in the groups receiving low and high dose contrast agents respectively [p=0.830], while at 7 days post-contrast it was 2.17+1.28 and 1.95+1.43 respectively in the two groups [p=0.391]. The contrast-induced reduction in renal function [rise in serum Cr >=0.5 mg/dl above base line] occurred in 14% [n=8] of patients in low dose and in 11% [n=7] in high dose contrast group [p=0.830, insignificant]. The results of our study confirm that high dose non-ionic contrast is not associated with increased risk of contrast-mediated nephrotoxicity in patients with pre-existing renal insufficiency undergoing cardiac angiography [p=0.830, insignificant]

Cutaneous maingestations of systemic lupus erythematosus in pakistani patients

Systemic Lupus Erythematosus [SLE] is an autoimmune process in which cutaneous lesions occur in majority of patients. This study from Karachi, Pakistan was conducted to determine the pattern and prevalence of such lesions in SLE in Pakistani patients. One hundred ninety eight patients with SLE fulfilling the clinical and laboratory criteria of the American Rheumatology Association were examined between 1986 and 2001' for the presence of cutaneous manifestations. Skin changes noted were: noncicatricial diffuse alopecia [22%], malar rash [31%], mucosal lesions [20%], discoid eruptions [15%], photosensitivity [33%], vascular lesions [20%], pruritis [17%], and pigmentary changes [22%]. Peripheral gangrene,chronic ulcers, Raynauds phenomenon, urticaria, chilblains, thrombophlebitis, palmar erythema, and erythema multiform were rare. Anti ANA and anti dsDNA were positive in 93% and 83% patients respectively. A different clinical pattern was noted in our patients than reported previously

Spetrum of complications and mortality of bacterial meningitis: an experience from a developing country

The aim of this study was to obtain data on predisposing factors, causative organisms and their associated mortality and complications related to acute bacterial meningitis. The chart review of all patients in whom acute bacterial meningitis was diagnosed at The Aga Khan University Hospital from January 1995 through December 2001. One hundred ninety-four patients were included in study. There were 146 males and 48 females. The mean age of our study population was 41 +/- 12.3 years. One hundred and ninety [97.9%] patients had communityacquired meningitis-, only 4 [2.0%] patients developed meningitis nosocomially. The two most common predisposing factors were diabetes mellitus [13.9%] and otitis media [7.7%] among all 194 patients. A significant proportion of patients with complications had diabetes mellitus [24.6%, p<0.001]. CSF and blood cultures were positive in 53 [27.3%] and 42 [21.6%] patients respectively-, there was no statistical difference found. The most common organisms isolated were Streptococcus pneumoniae in 35 [36.8%] patients followed by Neisseria meningitides in -30 [31.5%] -patients. Approximately 68% of -positive cultures -yielded S. pneumoniae and N. meningitides [p<0.0001]. The overall mortality rate was 22.1%. The mortality rate for Streptococcus pneumoniae was 17.1%. The highest mortality was observed in patients with Pseudomonal meningitis where all four patients expired followed by mortality rate of 85.7% in Escherichia coli afflicted patients [p<0.001]. Complications occurred in 73 [37.6%] patients with persistent complications in 31 [42.4%] patients. Complications resolved in 34 [46.5%] patients. The most common complications were seizures [12.8%] and cranial nerve palsies [11.3%]. Seizures were more likely to occur in older patients [p<0.05] whereas hydrocephalus was more common in younger patients [p<0.05]. Bacterial Meningitis remains a serious disease associated with substantial morbidity and mortality. Most cases are community acquired with S. Pneumoniae being the most common pathogen. Old age, diabetes mellitus, a positive culture, seizures as a complication and late stage in the disease are the important predictors of a poor outcome