Osteoporotic changes in Egyptian cirrhotic patients

Aim: Hepatic osteodystrophy occurs in most patients with chronic liver disease. Subjects and In this study, bone density, measured by dual energy X-ray absorptiometry [DEXA], and some biochemical markers of bone turnover were studied in 30 Egyptian schistosomal patients classified equally into 3 groups according to the Child-Pugh score of severity of liver disease. Patients showed significant reduction of BMD in both lumbar spine and femoral neck [LS: -2.87 +/- 1.39; FN: -0.54 +/- 1.13, p< 0.001]. Osteoporosis was found in 56.7% of patients. Urinary D-Pyr/cr, as a marker of bone resorption, showed marked significant increase in Child B and C patients [p<0.001], while serum B-AP and serum PICP, as markers of bone formation, showed less changes. Serum B-AP was significantly increased in the patient group [p<0.05], while serum PICP was insignificantly decreased in patients as compared to controls. The rate of bone loss, determined by the ratio of urinary D-Pyr/cr to PICP, was increased in Child A, B, and C patients. Serum testosterone was significantly decreased in both Child B and C patients and was markedly decreased in the whole patient group [p<0.001]. Conclusions: These results suggest that increased bone resorption is the predominant cause of hepatic osteodystrophy and its risk increases with the severity of liver disease. It also provides bone biomarkers as useful alternatives to bone biopsy in evaluating hepatic bone changes

Beta2 Microgolbulin amyloidsis in uremic patients

Aim: The aim of this work was designed to study some parameters of uremic- oxidant stress and their impact on the pathogenesis of dialysis- related amyloidosis. Subjects and This study was carried on 40 uremic patients and 10 normal subjects as control group [group l]. Patients were divided into 4 groups according to the duration of hemodialysis. Group II: 10 uremic patients on conservative treatment. Group III: 10 patients on hemodialysis for 1-5 years. Group IV: 10 patients on hemodialysis for 5-10 years. Group V: 10 patients on hemodialysis for more than 10 years. AII patients were subjected to thorough history taking, clinical examination, routine and specific laboratory investigations [plasma and tissue malonyldialdhyde, plasma advanced oxidation protein products, vitamin C and E and beta2 microglobulin concentration]. Histopathological study was done by light and electron microscope and histochemical assay for beta2 microglobulin in the affected tissue. plasma and tissue concentration of MDA were significantly higher among uremic non-dialysed and HD patients than in controls. Plasma AOPP were significantly higher in uremic non-dialysed and HD patients as compared to the control group. Plasma vitamin C was significantly lower in patients than in controls, while its oxidized product [dehydroascorbate] was significantly higher among the same groups as compared to the control group. Plasnma vitamin E was normal among all groups. It was significanthy inversely correlated with plasma MDA. PIasma beta2 M was significantly higher in uremic non-dialysed and HD patient as compared to the control group. Light and electrcon microscopical studies showed no amyloid deposits in group I and II, but in groups III, IV and V the incidence amyloid deposits were 10%, 40% and 70°, respectively. The prevalence of beta2 M amyloid in H patients was positively and significantly correlated to the duration of HD. Immunohistochemical study showed beta2 M deposition in all tissue specimens but the intensity of deposition was higher in uremic patients as compared i the control group. Conclusions: Oxidant-stress is well documented and clearly expressed both at the plasma and tissue levels in uremic and HD patients. It may have an important role in the pathogenesis of DRA through creating a state of carbonyl stress that modifies beta2M increasing its amyloidogenic tendency

Volume homeostasis in schistosomal patients with and without renal involvement

The aim of this study was studying some humoral and renal mechanisms controlling volume homeostasis during volume expansion and volume depletion among schistosomal patients with and without renal involvement. The subjects included in this study were ten non ascitic schistosomal patients [group A], another ten non ascitic proteinuric schistosomal patients [group B], ten control subjects [group C]. All groups were subjected to full history taking, clinical examination and investigations [stool analysis or rectal snip biopsy, urine analysis and urine protein estimation, renal function tests, liver function tests, hepatitis viral markers and percutaneous renal biopsy for nephrotic patients]. Experimental protocol included two studies: study I: this included infusion of isotonic saline [0.9%] in a dose of 40 ml/kg body weight over 30 minutes for acute volume expansion. Study 2: this included the administration of furosemide in a dose of 0.75 mg/kg body weight during one minute. The change in plasma volume after each study was calculated. Estimation of at rial natriuretic peptide [ANP] by radioimmunoassay basally and 1 hour after the study, plasma renin activity [PRA] and plasma aldosterone [PA] were done pre-study as well as, 1,2, and 3 hours post study. Fractional excretion of sodium, urinary sodium excretion rate, free water clearance as well as urinary flow rate were calculated before and after the study. Serum proteins and serum albumin were significantly lower in the schistosomal proteinuric group [group B]. Prothrombin activity showed a significant decrease in both groups A and B. All subjects of the three groups were negative for the studied viral markers. All nephrotic patients [group B] were biopsied and revealed membrano-proliferative type of glomerulonephritis. The percentage increase and decrease in plasma volume after volume expansion and depletion were comparable in the three studied groups with no significant difference. The basal ANP showed no significant difference between the three groups, it showed a significant rise especially in group B after volume expansion and a significant decline after volume depletion in the three groups. Schistosomal proteinuric patients [group B] showed incomplete suppression of PRA after volume expansion, there was a sustained rise in PRA and PA in schistosomal patients [group A] after volume depletion. The basal PA was significantly higher in schistosomal patients [group A] than the controls, it showed a significant decrease after volume expansion in the three studied groups. Fractional excretion of sodium showed a significant rise after volume expansion in the three studied groups, there was a significantly lower value in the first hour interval in all schistosomal patients [group A and B] than that of the control group[C], after volume depletion it showed a significant rise in the first and second hours only in all schistosomal patients [A and B]. Urinary sodium excretion rate showed a significant increase after volume expansion in the three studied groups, but the natriuresis was found to be impaired after the first hour in all schistosomal patients [group A and B] in comparison to the control subjects [group C]. After volume depletion,urinary sodium excretion rate showed a significant increase in the three studied groups. All schistosomal patients [group A and B] showed blunted natriuretic and diuretic response to furosemide when compared to the control group [C]. Free water clearance after volume expansion showed a significant rise in the first hour interval in group A, in the first and second hour interval in B and in the three hours intervals in C. After volume depletion there was no significant difference in the basal, first,second, and third hour interval values between the three groups. Urine flow rate increased significantly after volume expansion and diuretics in the three groups. All schistosomal patients [group A and B] showed significant lower values in the first and second hour after both volume expansion and depletion than the controls. ANP was involved in the regulation of blood volume in schistosomal patients with and without proteinuria. The high basal aldosterone levels in schistosomal patients may be related to impaired metabolic degradation rather than increased production. There was blunted natriuresis and diuresis in schistosomal patients early in the preascitic stage, this may be due to resistance to the properly released ANP. This resistance was related neither to its hypotensive action nor to hyperaldosteronism.The impaired urinary sodium excretion may be related to the increased tubular reabsorption. Schistosomal proteinuric patients tended also to retain sodium inspite of the proper hormonal response, so renal resistance may be a cause. Schistosomal patients tended to retain water and the ability to excrete free water was better in schistosomal proteinuric There was a state of diuretic resistance to furosemide in schistosomal patients with and without proteinuria