The effect of interferon alpha administration on acute attacks of familial Mediterranean fever: A double-blind, placebo-controlled trial.

BACKGROUND: About a quarter of familial Mediterranean fever (FMF) patients are partially or totally resistant to colchicine. A previous observation reported that acute attacks may be shortened by administration of interferon alpha (IFN). OBJECTIVE: We designed a double-blind, placebo-controlled trial to test our initial observations of a beneficial response with IFN in FMF attacks. METHODS: We treated 34 acute abdominal attacks with IFN 5 million IU or placebo sc in the early phase of the attack. Leucocytes, thrombocytes, the erythrocyte sedimentation rate, fibrinogen, C-reactive protein (CRP), serum amyloid A protein (SAA), haptoglobin, transferrin, IL-1beta and TNF-alpha were measured at hours 0, 6, 12, 24 and 48. RESULTS: The median time to recovery in those treated with IFN and placebo was not significantly different, while the leucocytosis and high levels of fibrinogen were significantly more prolonged in placebo-treated patients. CRP and SAA were extremely elevated and peaked at 24h, remaining less marked in the IFN-treated patients but the difference was not statistically significant. Observations regarding the other parameters were unremarkable. CONCLUSIONS: Although there were some clues indicating a depressed inflammatory response with IFN, we could not demonstrate a definitive effect of this agent in this double-blind trial. The drug may suppress the acute inflammation of FMF only if administered at the earliest phase. CRP and SAA may be more sensitive indicators of an attack than ESR or fibrinogen.

Levels of interleukin-6 (IL-6) and its soluble receptor (sIL-6R) in familial Mediterranean fever (FMF) patients and their first degree relatives.

OBJECTIVE: Familial Mediterranean Fever (FMF) is a hereditary disease characterized by recurrent inflammatory attacks. A subclinical inflammation may persist in periods between the attacks and heterozygotes may have higher than normal levels of acute phase proteins. We investigated the levels of interleukin-6 (IL-6) and its soluble receptor (sIL-6R) in FMF patients and their obligatory carrier relatives. METHODS: Serum levels of IL-6 and sIL-6R were measured during acute attacks (n = 18) and in attack-free FMF patients (n = 26), obligatory carriers of FMF (n = 17) and normal controls (n = 11). RESULTS: The median levels of IL-6 were significantly higher (45.71 pg/ mL, p = 0.001) during acute attacks of FMF only, and were normal (0.01 pg/ mL) in the other groups studied. There was no statistically significant difference in the median sIL-6R values between any of the groups (p = 0.22). CONCLUSION: IL-6 was extremely elevated during FMF attacks but could not detect hypothetical "subclinical" inflammation during attack-free intervals or in the heterozygote relatives of patients. Serum levels of sIL-6R were comparable in all four groups.

Investigation of relationship between idiopathic hypercalciuria and urinary enzyme activities.

In patients with uncomplicated idiopathic hypercalciuria renal function is normal except for increased renal calcium excretion. In this study, the level of fractional urinary enzyme excretion was assessed in relation to calciuria. Fourteen patients with a mean age of 5.8 +/- 0.8 years who had daily urinary calcium excretion more than 4 mg/kg and with otherwise normal renal function tests were included in the study. None of the patients manifested either renal calculus or nephrocalcinosis. Fourteen normal children with a mean age of 5.4 +/- 0.74 were included in the control group. The level of the urinary N-acetyl beta-D glucosaminidase (NAG) to creatinine ratio, fractional aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH) excretion were not significantly different compared to the control group (p > 0.05). The patients were subdivided according to the type of hypercalciuria. The levels of NAG/creatinine ratio, fractional ALT, AST, ALP, LDH excretion were not significantly different in the absorptive type of calciuria group compared to the control group (p > 0.05). In conclusion, hypercalciuria during childhood which is 6.46 +/- 1.83 mg/kg/day is not related to the levels of NAG/creatinine ratio, fractional ALT, AST, ALP and LDH excretion in urine.

Urinary N-acetyl-beta-D-glucosaminidase activity in rabbits with experimental hypercalciuria.

Routinely used renal function tests remain normal in uncomplicated hypercalciuria. The aim of this study was to assess the value of N-acetyl-beta-D-glucosaminidase (NAG), a sensitive marker of renal proximal tubular damage, in experimental hypercalciuria. Oral calcium providing 75 mg/kg per day elementary calcium and 20,000 IU/day vitamin D3 was administered for 15 days to 7 rabbits (Orytolagus cuniculus-New Zealand white) and 7 rabbits were given placebo as a control group. Serum calcium, phosphorus, and alkaline phosphatase, daily urinary calcium excretion and NAG/creatinine ratio were measured before and after drug administration. Kidneys were examined macroscopically and microscopically following the study period. Serum calcium, phosphorous and urinary calcium excretion increased, while alkaline phosphatase decreased significantly in response to drug treatment [10.8 +/- 1.5 vs. 12.2 +/- 1.3 mg/dl, 4.6 +/- 0.6 vs. 6.7 +/- 0.7 mg/ dl, 22.3 +/- 8.3 vs. 46.8 +/- 22.5 mg/kg per day, and 138.0 +/- 57.1 vs. 70.1 +/- 33.1 IU/l, respectively (P < 0.05)]. The NAG/creatinine ratio prior to the study (0.5 +/- 0.1 mU/ mg) was significantly different from that after the study (5.4 +/- 1.5 mU/mg, P < 0.01). In the control group, changes in serum and urinary parameters were not significant (P > 0.05). The relationship between the urinary NAG/ creatinine ratio and the daily urinary calcium excretion was statistically significant (r = 0.67, P < 0.05). In the study group, nephrocalcinosis was present in all rabbits except 1 (85.7%), whereas none of the control group rabbits had nephrocalcinosis. In conclusion, in rabbits urinary NAG excretion increases significantly in nephrocalcinosis induced by hypercalciuria.

Urinary enzyme changes in newborns with unconjugated hyperbilirubinemia.

Various changes in renal function caused by unconjugated hyperbilirubinemia in newborns have been suggested in previous reports. Disclosing an injury in renal tubulus epithelium is feasible by measurement of urinary enzymes. Thus, renal function tests and urinary enzymes in 25 terms newborns with unconjugated hyperbilirubinemia were evaluated before and after phototherapy. Ten healthy term newborns without hyperbilirubinemia formed the control group. Mean values of the variables obtained before and after phototherapy in the study group and in the controls were, respectively: urine osmolality (osm/kg H2O): 0.147 +/- 0.009, 0.174 +/- 0.011, and 0.153 +/- 0.018; endogenous creatinine clearance (mL/min per 1.73 m2): 45.7 +/- 2.15, 46.0 +/- 1.6 and 46.7 +/- 3.9; fractional excretion of sodium (%): 1.27 +/- 0.30, 0.79 +/- 0.19 and 1.24 +/- 0.07; tubular phosphorus reabsorption (%): 85.8 +/- 3.3, 87.8 +/- 2.8 and 86.6 +/- 1.7; urinary N-acetyl-beta-D glucosaminidase/creatinine (IU/mg): 0.617 +/- 0.226, 0.574 +/- 0.214 and 0.619 +/- 0.210; fractional excretion of alkaline phosphatase (%): 0.422 +/- 0.103, 1.001 +/- 0.374 and 0.596 +/- 0.201; fractional excretion of lactic dehydrogenase (LDH; %): 0.102 +/- 0.019, 0.121 +/- 0.023 and 0.119 +/- 0.041; fractional excretion of AST (%): 0.433 +/- 0.127, 0.530 +/- 0.113 and 0.502 +/- 0.074; fractional excretion of alanine aminotransferase (ALT; %) 0.856 +/- 0.413, 1.619 +/- 1.076 and 1.066 +/- 0.366. No significant difference was found between these values before and after phototherapy in the study group, or between the values before phototherapy in hyperbilirubinemic neonates and in the control group. In conclusion, unconjugated hyperbilirubinemia up to a serum level of 18.4 mg/dL in term neonates does not seem to result in injury of normal tubulus epithelium as shown by urinary enzyme levels.

Urinary enzyme changes in children undergoing cineangiographic evaluation using iopromid.

Nephropathy due to radiocontrast media presents with a wide spectrum of changes from reversible renal dysfunction to oliguria requiring dialysis. Nineteen patients (mean age 4.5 +/- 3.7 years) were included. Mean +/- SD values of the variables obtained before and 48 hours after angiography were the following: plasma creatinine: 0.6 +/- 0.10 and 0.6 +/- 0.16 mg/dl; endogenous creatinine clearance: 76.1 +/- 17.0 and 80.9 +/- 19.3 ml/min/1.73 m2; plasma osmolality: 279 +/- 23 and 298 +/- 39 mOsm/kg H2O; urine osmolality: 429 +/- 225 and 459 +/- 196 mOsm/kg H2O; fractional sodium excretion: 2.1 +/- 1.3% and 2.4 +/- 1.3%; plasma uric acid: 3.9 +/- 1.3 and 3.4 +/- 1.0 mg/dl; urinary AST/creatinine: 5.2 +/- 4.8 and 4.2 +/- 2.6 mU/mg; ALT/creatinine: 16.8 +/- 12.4 and 15.3 +/- 12.6 mU/mg; LDH/creatinine: 52.0 +/- 39.6 and 42.3 +/- 31.5 mU/mg; NAG/creatinine: 20.1 +/- 2.8 and 16.8 +/- 2.3 mU/mg, respectively. The changes in renal function parameters and urinary enzyme levels were insignificant statistically (p > 0.05). In conclusion, iopromid injection at maximum doses of 5 ml/kg does not result in injury to the tubular epithelium leading to increased urinary enzyme levels.