Insertion/deletion polymorphism in ACE gene as a predictor for progression of diabetic nephropathy.
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Biomedical subjects
Publications and source records attributed to S K Ha.
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Renal osteodystrophy has become a frequent complication in patients with chronic renal failure (CRF), and various histologic forms such as high turnover, low turnover and mixed bone disease have been demonstrated. The only reliable method for distinguishing patients with high turnover from those with low turnover bone disease is bone histomorphometric study, but its clinical utility is restricted. Because of its invasive nature, efforts have been made to predict indirectly the type and severity of this metabolic bone disease by serum assays. In this cross-sectional study, we measured total and regional (head, arms, trunk, ribs, legs, spine and pelvis) bone mineral densities (BMD) by dual X-ray absorptiometry (DXA) in patients with variable degrees of CRF and correlated them with various bone markers. Decreased BMDs were detected in various skeletal sites (trunk and pelvis) in the patients' group. Total BMD Z score was lower in predialysis CRF patients than in the control subjects. Decreased BMD Z scores on weight-bearing bone were pronounced at L1 lumbar vertebra, femur trochanter, femur neck and Ward's triangle. Positive linear correlations were found between creatinine clearance and trunk, ribs, pelvis, and spine BMDs. There were inverse linear correlations between total BMD and total BMD Z score and alkaline phosphatase (AP), urine deoxypyridinoline (U-DPD) in the patients' group. There were no correlations between regional and total BMD, total BMD Z score and serum calcium, ionized calcium, and serum phosphate. There were inverse linear correlations between BUN, creatinine and bone-specific alkaline phosphatase in the predialysis CRF group. We evaluated the correlations between intact parathyroid hormone (i-PTH) and biochemical and other bone markers. There was statistically significant linear correlation between i-PTH and AP. Other bone markers have no significant correlations with i-PTH. Our results demonstrated that there is significant bone loss in patients with CRF before the start of dialysis and also regional variations of BMDs in predialysis CRF patients. DXA is a useful method for evaluating regional and total BMDs and provides information about diverse regional skeletal changes. AP, i-PTH and U-DPD can predict BMD of predialysis CRF patients.
The aetiology and the pathophysiological mechanisms underlying the development of dry skin in uraemia are still unclear, but the hydration status of stratum corneum clearly influences the appearance of skin. The xerotic skin texture is often referred to as 'dry skin' and has been suggested as a cause of uraemic pruritus. To understand the aetiology of dry skin in uraemia we measured the status of skin surface hydration of uraemic patients with the corneometer and skin surface hydrometer, the functional capacity and the urea concentration of stratum corneum and the response of eccrine sweat gland to sudorific agent (0.05% pilocarpine HCL) in 18 age-matched haemodialysis patients and 10 healthy volunteers. We also performed the water sorption-desorption test to uraemic and control subjects after application of urea in various concentrations. Uraemic patient's skin showed decreased water content compared to control subjects. However, we found no correlation between dry skin and pruritus. Although the urea concentration of the horny layer in uraemic patients was elevated compared to control subjects (28.2 microgram/cm2 vs 5.04 micrograms/cm2, P < 0.05), its moisturizing effect to relieve pruritus is questionable because its artificial application revealed no improvement of the functional capacity of horny layer in concentration 5 times higher than the physiological concentration. Uraemic patients showed decreased sweating response to sudorific agent. In conclusion, the functional abnormalities of eccrine sweat glands may be account for dry skin in uraemic patients at least in part, but there is no correlation between xerosis and pruritus.
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We have done cross sectional and prospective studies to determine the prevalence and the clinical significance of antibodies to the hepatitis C virus (Anti-HCV) in 54 hemodialysis (HD) patients and 227 continuous ambulatory peritoneal dialysis (CAPD) patients. Fifteen patients (27.8%) were anti-HCV (+) among the HD group, and twelve patients (5.3%) were anti-HCV (+) among the CAPD group. In the HD group, the positivity of anti-HCV correlated with the duration of HD, but there was no significant correlation with the history of transfusion, the amount of transfusion and abnormal alanine aminotransferase (ALT). At the follow-up study in 164 cases (HD 50 cases, CAPD 114 cases) after 6 months, one of 14 anti-HCV (+) CAPD patients was converted to anti-HCV (-) and two of 35 anti-HCV (-) HD patients were converted to anti-HCV (+). In conclusion, the prevalence of anti-HCV was significantly higher in HD patients compared to CAPD patients, and the positivity for anti-HCV in HD patients correlated with the duration of HD. A regular follow-up of anti-HCV and isolation of anti-HCV (+) HD patients with a separate machine may be needed to prevent the transmission of the hepatitis C virus during hemodialysis.
To elucidate the nature of altered cellular immunity seen in patients with chronic renal failure, the values of interleukin-2 (IL-2), a kind of lymphokine, and T-cell colony forming units were measured in controls (N = 10), predialysis uremic patients (N = 14), patients undergoing chronic hemodialysis (HD, N = 11) and patients on continuous ambulatory peritoneal dialysis (CAPD, N = 9). Dialytic patients were selected as relatively stable cases receiving dialysis for more than 3 months. The duration of dialysis was 25.5 +/- 5.5 months in HD and 14.7 +/- 3.0 months in CAPD groups. The mean age was 30.3 years in the control, 36.1 years in the predialysis, 32.9 years in the HD and 41.1 years in the CAPD groups; all 4 groups showed male predominance. The serum creatinine concentration of each group was 1.2 +/- 0.1 mg/dl in the control, 14.1 +/- 0.9 mg/dl in predialysis, 13.5 +/- 1.3 mg/dl in HD and 14.7 +/- 0.9 mg/dl in CAPD groups. The level of IL-2 in the predialysis group was markedly lower compared to the control, HD and CAPD groups (as 3.1 +/- 0.8 unit vs. 8.8 +/- 2.2 unit, 11.8 +/- 3.0 unit and 14.9 +/- 3.4 unit, respectively, p < 0.05); the difference between the control and dialytic groups was not statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS)
The effect of captopril on proteinuria was evaluated in twenty patients with various glomerular diseases excreting heavy proteinuria (> 3.0 g/day). Captopril in a daily dose of 37.5 mg was administered orally three times a day to all patients and they were followed for eight weeks. Twenty-four hour urinary excretion of protein, creatinine, sodium, selective protein index (SPI), and blood chemistry including serum electrolytes were measured every two weeks. Twenty-four hour urinary protein excretion per gram creatinine started to fall within two weeks of captopril administration and became nearly stable after four weeks of therapy (p < 0.05). Mean 24-hour urinary protein excretion decreased significantly from a pretreatment value of 9.0 +/- 6.0 gm/gm of cr. to 4.4 +/- 3.5 gm/gm of cr. after eight weeks of captopril treatment. The serum albumin level increased progressively at six and eight weeks after the captopril treatment period and was significantly higher than the pretreatment value (p < 0.05). The decrease in proteinuria did not coincide with a fall in blood pressure or any changes in creatinine clearance. We conclude that captopril does have a significant antiproteinuric effect in patients excreting heavy proteinuria with various glomerular diseases. However, the long term therapeutic efficacy and any renal protective effect of this drug remain to be proven.
The effects of several ionophores on renin secretion were investigated in rabbit renal cortical slices. When slices were incubated in the absence of Ca++, the K+ ionophore valinomycin (10(-5) approximately 5 x 10(-4) M) or the monovalent cation ionophore nonactin (10(-4) M) stimulated renin secretion about 2-fold. The renin secretion stimulated by valinomycin was further increased by inclusion of the H+ ionophore, carbonylcyanide m-chlorophenylhydrazone. The electroneutral K+/H+ exchange ionophore nigericin (10(-5) approximately 5 x 10(-4) M) stimulated renin secretion in a dose-dependent manner, producing a maximal stimulation of about 17-fold. Another electroneutral exchange ionophore, monensin, also significantly stimulated secretion. The stimulation by both valinomycin and nigericin was apparent whether slices were incubated in Na(+)-rich or K(+)-rich media. The extent of stimulation by the two ionophores was dependent upon the presence of anion with acetate greater than Cl greater than isethionate greater than thiocyanate. Thiocyanate itself markedly inhibited renin secretion. Incubating of slices in an iso-osmotic ammonium acetate medium which is known to induce rapid swelling of secretory granules, stimulated renin secretion to the magnitude comparable to that of maximal stimulation by nigericin in a potassium acetate medium. The pattern of response to these ionophores indicates that changes in K+, H+ and anion gradients across the renin secretory granule may modulate renin secretory rate. It is proposed that conditions which allow accumulation of K+ and anion within acidic renin secretory granules lead to osmotic swelling of the granules and that granule swelling may promote exocytosis.
We performed an epidemiological study of the hepatitis C infection on 112 patients of 3 urban hemodialysis units using a recently developed anti-HCV recombinant based assay. Eleven patients (9.8%) were positive for anti-HCV. Among them, 8 (72.7%) were positive for anti-HBc, one of whom was HBsAg positive and 6 of whom were also anti-HBs positive. Surprisingly, all of the anti-HCV (+) patients were normal alanine aminotransferase. The mean age of the anti-HCV (+) patients was 50.7 +/- 3.3 (mean +/- SE) and that of the anti-HCV (-) was 47.6 +/- 1.3. The mean duration (month) of hemodialysis of the anti-HCV (+) and anti-HCV (-)groups were 52.7 +/- 7.2 (mean +/- SE) and 60.9 +/- 9.7, respectively. The prevalence of anti-HCV among anti-HBc positive subjects was 9.5% and that among anti-HBc negative subjects was 17.6%. This didn't have any statistical significance according to the criteria of the study (p = 0.308). The prevalence of anti-HCV among the transfusion positive group was 11.0% and that of the transfusion negative group was 7.7%. This data showed the tendency for a higher prevalence of anti-HCV among the transfusion positive group, but this also didn't reach statistical significance (p = 0.424). Of the 40 normal controls, none were anti-HCV positive. The prevalence of HBsAg in our hemodialysis units was 12.5%. This rate was not so much higher than the average population in Korea. The prevalence of anti-HCV and previous hepatitis B virus infection also had no significant relationship.(ABSTRACT TRUNCATED AT 250 WORDS)
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OBJECTIVE: To assess the nature of the decline in residual renal function (RRF) after the initiation of peritoneal dialysis, and to identify risk factors influencing the preservation of RRF. DESIGN: A retrospective single-center study. SETTING: Tertiary medical center. PATIENTS: Eighty patients who were clinically stable and had been on continuous ambulatory peritoneal dialysis (CAPD) for a minimum of 6 months. MAIN OUTCOME MEASURES: All subjects had at least three measurements of RRF, which was calculated as the average of creatinine clearance (Ccr) and urea clearance from a 24-hour urine collection. All measurements of RRF were plotted on a logarithmic scale and a linear scale against the duration of CAPD. Covariables used in the correlation analyses were age, sex, the presence of diabetes mellitus, mean blood pressure, mean diastolic blood pressure, hematocrit and Ccr at the start of peritoneal dialysis, peritoneal membrane transport characteristics by peritoneal equilibration test (PET), and the rate of peritonitis. RESULTS: A significant correlation was found between CAPD duration and RRF decline represented on a logarithmic scale with a correlation coefficient (r) of 0.355 (p < 0.001). In contrast, on a linear scale, the correlation coefficient was only 0.273 (p < 0.01). By linear multiple regression analysis, the only independent risk factor for the decline of RRF was the rate of peritonitis (r = -0.446, p < 0.001). CONCLUSION: These results suggest that RRF declines exponentially rather than linearly with time, and that the rate of peritonitis is an independent risk factor for the decline of RRF in CAPD patients.