bluuebunny/crossref_metadata_2025 huggingface dataset:
Interferon Therapy for Chronic Hepatitis C in Hemodialysis Patients: Increased Serum Levels of Interferon
Authors: Uchihara Masakatsu , Izumi Namiki , Sakai Yoshinori , Yauchi Tsunehito , Miyake Shozo , Sakai Takahiro , Akiba Takashi , Marumo Fumiaki , Sato Chifumi
Published: April 2003

Background/Aims: The efficacy and side effects of interferon (IFN) therapy have not been well clarified in hemodialysis patients with chronic hepatitis C. Methods: In 6 of 9 hemodialysis patients with chronic hepatitis C, 3 million units (MU) or 6 MU of recombinant IFN-α2b or natural IFN-α were administered intramuscularly daily for the first 2 weeks, followed by three times a week for 22 weeks. In the remaining 3 patients, 3 MU of IFN-α2b were given three times a week for 24 weeks. Serum concentrations of IFN-α2b were measured sequentially after the injection of interferon. Responders were defined as the patients with normal serum aminotransferase and negative serum HCV RNA 6 months after the cessation of IFN therapy. Results: Three of the 6 patients who were administered IFN daily in the first 2 weeks were responders, while the other 3 withdrew from the therapy due to serious adverse events such as depression, loss of consciousness and persistence of high-grade fever. Serious adverse events were not observed in the 3 patients without daily administration. Half-lives of IFN-α2b in hemodialysis patients were significantly longer than those in nonuremic patients (10.0 vs. 6.0 h, p < 0.05). Moreover, the areas under the serum concentration curve of the hemodialysis patients were significantly larger than those of nonuremic patients (756 ± 223 vs. 324 ± 223 IU·h/ml, p < 0.05), despite the fact that the dose of IFN-α administered to hemodialysis patients was half that administered to nonuremic patients. Conclusions: In hemodialysis patients with chronic hepatitis C, pharmacokinetic parameters of IFN may be different from those in nonuremic patients, and daily or high-dose administration of IFN may lead to serious adverse events in those patients.
Paper Chromatography prior to Cortisol RIA Allows for Accurate Use of the Dexamethasone Suppression Test in Chronic Renal Failure
Authors: van Herle A.J. , Birnbaum J.A. , Slomowitz L.A. , Mayes D. , Chandler D.W. , Rosenblit P.D. , Nissenson A.
Published: April 2003

The assessment of the hypothalamic-pituitary-adrenal axis in patients with chronic renal failure (CRF) on hemodialysis is often hampered by abnormal responses to the standard 1-mg dexamethasone suppression test. Various mechanisms have been proposed to explain this lack of suppressibility. The present study was designed to look into the mechanisms possible for these findings in patients with CRF. We studied 6 patients with CRF on hemodialysis and 5 healthy subjects utilizing the 1-mg dexamethasone suppression test as well as the 50-mg hydrocortisone suppression test. Samples were assayed for dexamethasone, adrenocorticotropic hormone, corticosterone, and cortisol by both direct radioimmunoassay (RIA) and RIA after paper chromatography. Utilizing the direct cortisol RIA, 4 of 6 patients with CRF exhibited blunted dexamethasone suppression, while all 6 patients showed normal suppressibility after dexamethasone when cortisol was measured after paper chromatography. In contrast, all controls showed normal suppressibility regardless of the cortisol assay procedure used. The hydrocortisone suppression test was unreliable in the setting of CRF. Mean dexamethasone levels were similar in both groups. Plasma adrenocorticotropic hormone levels were significantly higher in the CRF patients, possibly indicative of an underlying hypothalamic-pituitary-adrenal axis abnormality. Abnormalities in dexamethasone suppression testing in patients with CRF may be explained by the overestimation of cortisol levels by direct RIA rather than by alteration of dexamethasone absorption or metabolism. Measurement of cortisol after paper chromatography is superior to direct RIA of cortisol in patients with CRF.
Different Actions of the Cyclooxygenase 2 Selective Inhibitor Flosulide in Rats with Passive Heymann Nephritis
Authors: Heise Gunhild , Grabensee Bernd , Schrör Karsten , Heering Peter
Published: April 2003

The prostaglandin cyclooxygenase (Cox) exists in two isoforms with different genetic representation. The isoform, which is constitutively expressed (Cox 1), and mediates physiological functions of prostaglandins, and the inducible isoform (Cox 2) which is upregulated by inflammatory stimuli. This study attempts to determine whether a Cox 2 selective inhibitor, flosulide, differs from the mixed type Cox 1 and Cox 2 inhibitor aspirin in respect of renal function and eicosanoid excretion in experimental nephritis. The effects of flosulide and aspirin were studied during the autologous phase of passive Heymann nephritis (PHN) in rats. Female Wistar rats were injected i.v. with 1 ml of Fx1A antiserum at day 1. From day 7 to day 14 they received either aspirin (aspirin, 50 mg/day), flosulide, (0.75 mg/day) or vehicle p.o. The kidney function was evaluated and the animals sacrificed. The kidneys were removed and glomeruli isolated. The glomeruli were incubated in physiological buffer solution. Basal prostaglandin generation was determined in the supernatant. Treatment with flosulide significantly reduced proteinuria as compared to aspirin treatment (64±15 vs. 109±14 mg/24 h, p < 0.05). Plasma protein and albumin levels were significantly lower in the aspirin-treated group than in flosulide-treated animals (4.7±0.26 vs. 5.48±0.08 mg/dl, p < 0.05 and 0.96±0.04 vs. 1.25±0.10 mg/dl, p < 0.05). Glomerular prostaglandin production (6-keto-PGF1α, TxB2, Bicyclo-PGE2) was significantly reduced in aspirin-, but not in flosulide-treated animals. This was mainly due to a reduction of glomerular TxB2 production by aspirin. Our data demonstrate that a Cox 2 selective inhibitor of prostaglandin formation, flosulide, has beneficial effects on preservation of kidney function in rats with PHN, whereas aspirin has not. These beneficial effects of flosulide possibly result from preservation of the physiological glomerular prostaglandin production. Thus, selective Cox 2 inhibitors might be interesting substances for treatment of nephrotic syndrome.
Plasma and Urinary Levels of Adrenomedullin in Chronic Glomerulonephritis Patients with Proteinuria
Authors: Kubo Atsushi , Kurioka Hideyuki , Minamino Naoto , Nishitani Yoshiharu , Sato Hiroaki , Nishino Toshihiko , Iwano Masayuki , Shiiki Hideo , Kangawa Kenji , Matsuo Hisayuki , Dohi Kazuhiro
Published: April 2003

In this study, we measured levels of plasma and urinary adrenomedullin (AM) in 37 patients with chronic glomerulonephritis including minimal change nephrotic syndrome, focal segmental glomerulosclerosis or membranous nephropathy that can induce severe proteinuria. Thirty-nine healthy volunteers were enrolled as controls. Plasma and urinary AM levels were measured by an AM-specific radioimmunoassay. Plasma AM concentrations were higher and urinary AM levels were lower in patients with chronic glomerulonephritis than in healthy volunteers. Patients were divided into two groups according to urinary excretion of protein for 24 h (UPro, g/day) which reflects the disease activity or glomerular damage of the glomerulonephritis (group I: Upro < 1, group II: Upro ≥ 1). Plasma AM levels positively and urinary AM-levels negatively correlated with the degree of proteinuria. These results suggest that plasma and urinary AM levels in patients with chronic glomerulonephritis reflect the disease activity or glomerular damage represented by the degree of proteinuria.
Hypertension in the Transplanted Patient
Authors: Zeier M. , Mandelbaum A. , Ritz E.
Published: April 2003

Hypertension is a common finding after renal transplantation, and it has a variety of underlying mechanisms. One reason is the type of immunosuppressive therapy, with a higher prevalence of hypertension in cyclosporine-treated patients. Cyclosporine interferes with several humoral and neural systems which are involved in blood pressure regulation such as the renin-angiotensin system, endothelins, nitric oxide, prostaglandins and the sympathetic nervous system. Other pathomechanisms for posttransplant hypertension are uncontrolled renin secretion of the native kidneys, polycythemia, recurrence of renal disease in the graft and renal failure. Renal transplant artery stenosis is a potentially treatable cause of post-transplant hypertension and several techniques such MRT angiography, Doppler sonography and conventional angiography are available. The diagnosis and treatment of hypertension are of high importance in general for the transplanted patient, and especially for the long-term prognosis of graft function.
Coronary Artery Diameter and Left Ventricular Function in Patients on Maintenance Hemodialysis Treatment: Comparison between Diabetic and Nondiabetic Patients
Authors: Hatada K. , Sugiura T. , Nakamura S. , Kamihata H. , Fujimoto T. , Baden M. , Takahashi N. , Iwasaka T.
Published: April 2003

Background/Aims: This study examined the role of diabetes mellitus on determining left ventricular function by evaluating coronary artery diameter in patients with end-stage renal disease on maintenance hemodialysis treatment. Methods: We studied 12 diabetic and 12 nondiabetic patients on maintenance hemodialysis treatment without significant stenoses of the major epicardial coronary arteries. Patients were matched for age, sex distribution, duration of dialysis and incidence of major coronary risk factors. Left ventricular wall thickness (septal and posterior walls) and left ventricular diameter (end-diastolic and systolic phases), were measured by echocardiography. Hemodynamic measurements and coronary angiography were performed on the day of hemodialysis and coronary artery diameter at the proximal and mid portion of three major coronary arteries were measured using the computed densitometry method. Results: Right and left anterior descending and circumflex coronary artery diameters were all significantly smaller and the frequency of coronary artery calcification was higher in diabetic (58%) compared to nondiabetic (8%) patients. Although there were no significant differences in left ventricular wall thickness, left ventricular diameter, mean right atrial pressure and cardiac index between the two groups, left ventricular end-diastolic pressure was significantly higher in diabetic (22 ± 9 mm Hg) compared to nondiabetic patients (14 ± 5 mm Hg). Conclusion: Despite that there were no significant stenoses of the major epicardial coronary arteries, diffuse luminal narrowing of the epicardial coronary arteries in diabetic patients on maintenance hemodialysis treatment was associated with increased left ventricular end-diastolic pressure.
Glomerular Hypertrophy as a Prognostic Marker in Childhood IgA Nephropathy
Authors: Tóth Tibor , Takebayashi Shigeo
Published: April 2003

A clinicopathological and morphometric analysis of glomerular hypertrophy (GH) was conducted using biopsies obtained from 52 selected pediatric patients with IgA nephropathy (IgAN). Of the 52 patients, consisting of 12 with chronic renal failure (CRF) and 40 without CRF, various clinical and morphometric parameters were compared to 10 controls with benign hematuria. The mean glomerular tuft size, mesangial area, and interstitial area all significantly increased in patients with poor prognosis when compared to the non-CRF-IgAN cases and the control cases. The glomerular capillary loop size was also significantly greater in CRF-IgAN than in non-CRF-IgAn patients (1.37 times) and the controls (1.55 times). The 10-year renal survival rates of patients with ‘large’ loop size (>1.55-fold) were significantly lower (p < 0.001) than those of patients with a smaller capillary loop size. The size of the capillary loops was directly related to the relative interstitial area (Aint) (r2 = 0.43, p < 0.001), to the degree of glomerulosclerosis (GS; r2 = 0.348, p < 0.001) and the mesangial area (r2 = 0.326, p < 0.001). Proteinuria tightly correlated with the capillary loop size (r2 = 0.374, p < 0.001). It was not unexpected that a strong relationship was detected between the serum creatinine level and Aint (r2 = 0.452, p < 0.001) and the percentage of GS (r2 = 0.342, p < 0.001). In IgAN the percentage of GS correlated significantly with Aint (r2 = 0.484, p < 0.001). GH, which was manifested by glomerular capillary loop dilatation, shows a close correlation with the interstitial expansion, degree of GS and mesangial enlargement. These data suggest that both extra- and intraglomerular hemodynamic changes followed by primary glomerular damage thus lead to capillary dilatation of the intact glomeruli as a morphological manifestation of GH and therefore such changes play a key role in the progression of IgAN.
Estrogen Replacement Therapy with Its Physiological Dose Does Not Eliminate the Aggravating Effect of Ovariectomy on Glomerular Injury in Hypercholesterolemic Female Imai Rats
Authors: Sakemi Takanobu , Tomiyoshi Yoshiyuki , Miyazono Motoaki , Ikeda Yuji
Published: April 2003

Hypercholesterolemic Imai rats spontaneously develop proteinuria and glomerulosclerosis, especially in males. Estrogen administration attenuated glomerular injury in male Imai rats, and the aggravating effect of ovariectomy in female rats is found. To clarify whether this aggravating effect of ovariectomy is due to a lack of estrogen, we administered estrogen to ovariectomized female Imai rats. At 6 weeks of age, group 1 (control) was sham-operated and group 2 was ovariectomized. Groups 3 and 4 were ovariectomized and received estrogen replacement therapy (0.1 mg in group 3 and 0.2 mg in group 4 once a month subcutaneously). Body weight, urinary protein and serum constituents were investigated every month from 3 to 6 months of age. At 6 months of age, rats were studied morphologically. Estrogen replacement therapy increased serum estrogen to levels close to those of controls when 0.1 mg was used, or higher when 0.2 mg was used. Estrogen replacement therapy with 0.1 mg did not eliminate the aggravating effect of ovariectomy on glomerular injury and rather aggravated it, but conversely therapy with 0.2 mg attenuated glomerular injury and abolished the aggravating effect of ovariectomy. Estrogen replacement therapy markedly elevated serum GH levels dose-dependently. These results suggested that other hormones as well as estrogen may play a protective role of the ovary for the development of glomerular injury, and that estrogen seems to exert a dual effect on glomerular injury.
Quantitative Assessment of HCV Load in Chronic Hemodialysis Patients: A Cross-Sectional Survey
Authors: Fabrizi F. , Martin P. , Dixit V. , Brezina M. , Cole M.J. , Gerosa S. , Vinson S. , Mousa M. , Gitnick G.
Published: April 2003

Recent evidence has been accumulated showing that chronic hemodialysis (HD) patients have a very high prevalence of antibodies to hepatitis C virus (HCV). In contrast, there is little information addressing the virological characteristics of HCV infection in this population. Aim: To measure HCV viral load and to correlate this with demographic, biochemical, and clinical features of a large cohort of HCV-infected patients on chronic HD. Methods: 394 chronic HD patients were tested by branched-DNA signal amplification assay, anti-HCV enzyme-linked immunosorbent assay 2.0, and on the basis of the aspartate aminotransferase/alanine aminotransferase (AST/ALT) activity. Multivariate analysis by ordinal logistic regression model was performed: age, gender, race, time on HD, allocation of the patients among the HD units, etiology of end-stage renal disease, HBsAg status, anti-HCV positivity, HCV genotype, and AST/ALT levels were independent factors, and viremic levels of HCV in serum were assumed as dependent variables. Results: 88 (22.3%) patients showed serological and/or virological signs of HCV infection. 59 (15%) out of 394 had detectable HCV RNA in serum, the mean HCV load was 19.4 × 105 (95% CI, 6.06 × 107 to 6.2 × 104) Eq/ml. According to the criteria suggested by others [J Infect Dis 1994;169:1219–1225], there were 8 (13.5%) individuals with high-titer viremia (>1 × 107 Eq/ml) in the subset of viremic patients. A small subset (8/394 or 2%) of individuals was seronegative, but viremic; 29 (7%) out of 394 were seropositive without detectable HCV RNA in serum. Univariate analysis showed that the frequency of anti-HCV positivity was significantly higher in viremic patients as compared with individuals with no detectable HCV viremia: 51/59 (86%) vs. 29/335 (8.6%), p = 0.0001. Serum AST and ALT levels were significantly higher in viremic patients than in individuals with no detectable HCV RNA in serum: 23.8 (95% CI 60.8–9.3) vs. 17.1 (95% CI 50.4–5.8) U/l (p = 0.009) and 14.4 (95% CI 48.9–4.3) vs. 9.8 (95% CI, 37.3– 2.5) U/l (p = 0.008). Logistic regression analysis showed an association between HCV viremia and anti-HCV positivity (p = 0.00001) and ALT activity (p = 0.01). Conclusions: Hepatitis C virus infection is highly prevalent in the HD population; the viral load is relatively low, and it was associated with elevated hepatic enzyme levels and anti-HCV positivity. No other clinical characteristics were associated with HCV RNA levels. Seronegative but viremic patients were also found. Longitudinal studies with long follow-up periods are necessary to evaluate the course of HCV load over time in this population.
Coexpression of Collagens and Collagen-Binding Heat Shock Protein 47 in Human Diabetic Nephropathy and IgA Nephropathy
Authors: Razzaque M.S. , Kumatori A. , Harada T. , Taguchi T.
Published: April 2003

The mechanism of structural changes of the kidney in human diabetic nephropathy (DN) and IgA nephropathy (IgAN) is not yet completely known, but excessive deposition of extracellular matrix (ECM), including various collagens, may be crucial to this process. Heat shock protein (HSP) 47 has been identified as collagen-binding stress protein, shown to have a specific role in the intracellular processing of procollagen molecules during collagen assembly. To determine whether increased deposition of collagens in human DN and IgAN is related to HSP47, we investigated the expression of HSP47 in renal biopsy and autopsy sections obtained from 22 DN and 45 IgAN patients. Five renal biopsy specimens, diagnosed as minor glomerular abnormalities, were simultaneously studied as controls. Monoclonal antibodies specific for HSP47, type III collagen and type IV collagen were used to assess the relative expression of their proteins in paraffin-embedded renal sections by immunohistochemistry. Increased deposition of collagens was closely related to the sclerotic activity of the disease process in DN and IgAN; increased deposition of collagens was often present in relation to a strong expression of HSP47, a stress protein known to regulate collagen synthesis/assembly. By double immunostaining, we found colocalization of collagens and their molecular chaperone HSP47 in the sclerotic glomeruli and tubulointerstitium in DN and IgAN. Our results strongly support a pathologic role for HSP47 in both these diseases and that increased levels of HSP47 may play an important role in the excessive assembly of collagens resulting in glomerulosclerosis and interstitial fibrosis found in DN and IgAN patients.
Hypertension as an Etiopathological Factor in the Development of Cerebral Atrophy in Hemodialyzed Patients
Authors: Savazzi Giorgio M. , Cusmano Ferdinando , Bergamaschi Enrico , Vinci Simonetta , Allegri Landino , Garini Giovanni
Published: April 2003

Twenty-five patients on long-term regular hemodialysis treatment (RDT) at our dialysis unit who underwent diagnostic cerebral computed tomography (CCT) participated in a study aimed at clarifying the pathogenesis of cerebral atrophy occasionally found at their original scan. The upper age limit was 55 years to exclude the physiological involutive brain changes occurring with age. Cerebral atrophy (CA), as defined morphologically (enlargement of cerebral sulci or an increased Evan’s Index), was detected in all cases. Seventeen patients underwent magnetic resonance imaging (MRI) to define possible white matter changes more accurately. No significant correlation was found between the degree of atrophy and the following uremia-altered hematoseric parameters: creatinine, hematocrit, cholesterol, triglyceridemia, albumin, PTH, calcium, inorganic phosphate. There was no correlation between degree of atrophy and number of months the patients had been on RDT or time that passed between the finding of a creatinine clearance <30 ml/min and the start of RDT. Very high correlations were found between the degree of CA and predialytic blood pressure values, and between CA and the duration of hypertension (n = 13, r = 0.66, p < 0.013). Thus, hypertension seems to be an early cause of cerebral parenchymal damage in RDT patients, and should be promptly corrected.
Preexisting Membranous Nephropathy in Allograft Kidney
Authors: Nakazawa Koh , Shimojo Hisashi , Komiyama Yuichi , Itoh Nobuo , Katai Miyuki , Hashizume Kiyoshi , Shigematsu Hidekazu
Published: April 2003

A case of membranous nephropathy, preexisting in a donor kidney, will be reported. A 41-year-old man underwent a cadaver renal transplantation. An allograft biopsy specimen obtained during the operation showed spike formation on periodic acid-silver methenamine staining and deposition of IgG along the glomerular capillary loop on immunoperoxidase staining. Immunofluorescence staining for IgG remained in the specimens obtained on day 11 and after 4 weeks, but markedly decreased in the specimen obtained 7 weeks after transplantation. Electron-dense deposits also decreased in amount, but irregular thickening of the glomerular basement membrane with spikes, electron-lucent washout lesions, and small amounts of electron-dense deposits remained 20 months after the transplantation. These findings suggest that membranous nephropathy, as well as IgA nephritis and diabetic nephropathy, resolve after renal transplantation and that deposition of IgG markedly decreases within a few months after transplantation, but that complete histological restoration of the basement membrane needs at least a few years.
Renal Function in Cyanotic Congenital Heart Disease
Authors: Burlet Anne , Drukker Alfred , Guignard Jean-Pierre
Published: April 2003

We performed renal function tests in 18 young patients, 1.8–14.6 years of age, with cyanotic congenital heart disease (CCHD). Glomerular filtration rate was normal (116 ± 4.5 ml/min/1.73 m2), and renal plasma flow was decreased (410 ± 25 ml/min/1.73 m2) with a rise in the filtration fraction (29 ± 1.1%). The suggested pathophysiologic explanation of these findings is that the blood hyperviscosity seen in patients with CCHD causes an overall increase in renal vascular resistance with a rise in intraglomerular blood pressure. Despite a sluggish flow of blood in the glomerular capillary bed, the effective filtration pressure was adjusted to conserve the glomerular filtration rate. In addition to these renal hemodynamic parameters, we also studied renal acidification and tubular sodium and water handling during a forced water diuresis. Our data indicate that children with CCHD have a mild to moderate normal ion gap metabolic acidosis due to a low proximal tubular threshold for bicarbonate. Proximal tubular sodium and water reabsorption under these conditions were somewhat increased, though not significantly, probably due to intrarenal hydrostatic forces, in particular the rise in the oncotic pressure in the postglomerular capillaries in patients with high hematocrit values. The distal tubular functions such as sodium handling and acidification were not affected.
Phyllanthus niruri Inhibits Calcium Oxalate Endocytosis by Renal Tubular Cells: Its Role in Urolithiasis
Authors: Campos Alexandre H. , Schor Nestor
Published: April 2003

We investigated the in vitro effect of an aqueous extract of Phyllanthus niruri L. on a model of CaOx crystal endocytosis by Madin-Darby canine kidney cells. The extract exhibited a potent and effective non-concentration-dependent inhibitory effect on the CaOx crystal internalization. This response was present even at very high (pathologic) CaOx concentrations and no P. niruri L.-induced toxic effect could be detected. Biochemical analysis of culture media containing P. niruri L. did not provide any clues for the elucidation of the cellular pathways affected by this natural product. Although further studies are necessary for a better understanding of the role of P. niruri L. in urolithiasis, our findings show that this natural product could be an attractive alternative for the treatment of urinary stones.
Pentanucleotide Repeat and Size Polymorphisms in the Apolipoprotein(a) Gene Are Associated with the Lipoprotein(a) Concentration in Chronic Hemodialysis Patients
Authors: Tanaka Mari , Yanagi Hisako , Ando Ryoichi , Kurihara Satoshi , Hirano Chiaki , Kobayashi Kimiko , Kikuchi Shuichi , Hamaguchi Hideo , Tsuchiya Shigeru , Tomura Shigeo
Published: April 2003

The elevation of serum or plasma lipoprotein(a) [Lp(a)] levels is regarded as an independent risk factor for cardiovascular disease, and many previous reports demonstrated that Lp(a) levels in hemodialysis patients were significantly higher than in controls. The purpose of this study was to investigate the effect of a pentanucleotide repeat polymorphism [(TTTTA)n] in the 5′-flanking region of the apolipoprotein(a) [apo(a)] gene and of a size polymorphism of apo(a) for elevated Lp(a) concentrations observed in chronic hemodialysis patients. We studied 172 patients on chronic hemodialysis and 199 healthy adults. For analysis of the pentanucleotide repeat polymorphism, polymerase chain reaction products were loaded on polyacrylamide gel for electrophoresis. apo(a) size phenotyping was performed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting. The median level of Lp(a) in the patients was 14.2 mg/dl which was significantly higher than that in controls (12.0 mg/dl; p < 0.05). In the genotype of (TTTTA)8/8, the median Lp(a) level in the patients (15.9 mg/dl) was significantly higher than that in controls (13.0 mg/dl; p < 0.05). In the genotype of (TTTTA)8/8 with large-sized apo(a) isoforms (A16–A25), the patients had significantly higher Lp(a) levels than the controls (p < 0.05). In conclusion, increased Lp(a) levels in chronic hemodialysis patients were mainly attributed to the combination of eight repeats of the pentanucleotide polymorphism and large-sized isoforms of apo(a).
Exercise Coaching and Rehabilitation Counseling Improve Quality of Life for Predialysis and Dialysis Patients
Authors: Fitts Sally S. , Guthrie Mark R. , Blagg Christopher R.
Published: April 2003

Advances in medical treatment have improved the rehabilitation potential of predialysis (P) and dialysis (D) patients, but deficits remain in their physical and vocational functioning. We studied 18 P (expected to begin dialysis in 6–12 months) and 18 D patients (on dialysis 1–5 years) for 1 year. Exercise coaching and rehabilitation counseling were provided at no cost for the first 6 months to half of each patient group (rehabilitation group = R); the other half were assigned randomly to controls (C). No R services were provided during 6 months of follow-up. PR walked further in 6 min at 6 months (+3.9 m) and 12 months (+4.1 m) than initially (p < 0.01). Hematocrit increased in R (p < 0.05), but not in C. Symptom scores were stable in D, worsened 21% in PC, and improved 15% in PR. Sickness impact profile scores were better in PR than PC at 6 months (p < 0.05) and 12 months (NS). Comorbidity correlated with symptoms (r = +0.34, p < 0.05), self-rated affect (r = –0.35, p < 0.05), and self-rated Karnofsky index of disability (r = –0.37, p < 0.05), but not with physician-rated affect or physician-rated Karnofsky index of disability. Thus, quality of life was stable or improved in PR, but declined in PC; PR benefited more than DR. Rehabilitation services are more beneficial before than after patients stabilize on dialysis, and quality of life monitoring should continue indefinitely.
Discordant Evolution of Asymptomatic Proteinuria in Identical Twins
Authors: Kim Hye Young , Oh Ha-Young , Lee Yoon Ha , Huh Wooseong , Kim Yoon-Goo , Kim Dae Joong , Ko Young Hyeh , Kim Mi Kyoung
Published: April 2003

We describe a pair of 17-year-old identical twin brothers with asymptomatic proteinuria, one of whom showed focal segmental glomerulosclerosis (FSGS) while the other showed immunoglobulin M (IgM) nephropathy. For each twin, audiological examination was normal. There was no family history of renal failure, deafness, or hematuria. HLA typing revealed an identical phenotype consisting of A25, A33, B44, B54, Cw1, Cw7, DR7 and DRB1. There is still controversy about whether minimal change disease, IgM nephropathy, and FSGS are discrete entities or different aspects of the same disease. The coexistence of IgM nephropathy and FSGS in identical twins suggests that the same genetic factors may be involved in the development of both diseases. However, although the brothers are identical twins, they had different eating habits and body weight. The twin who preferred to eat a protein-rich diet and who was heavier developed early proteinuria and manifested FSGS on renal biopsy. The discordant evolution of asymptomatic proteinuria in identical twins may provide a clue for the existence of environmental factors on the progression from IgM nephropathy to FSGS. Therefore, this report provides indirect support for the hypothesis that IgM nephropathy and FSGS represent different aspects in the spectrum of a single disease.
Effects of Mediterranean Diet on Lipid Levels and Cardiovascular Risk in Renal Transplant Recipients
Authors: Barbagallo C.M. , Cefalù A.B. , Gallo S. , Rizzo M. , Noto D. , Cavera G. , Rao Camemi A. , Marino G. , Caldarella R. , Notarbartolo A. , Averna M.R.
Published: April 2003

Background: Renal transplant recipients have an increased incidence of cardiovascular disease. These patients present abnormalities of lipoprotein profile which are persistent and involve an increasing number of individuals, suggesting the opportunity of an early therapeutic intervention. Methods: We evaluated the effects of a 10- to 12-week diet based on the American Heart Association step-one diet criteria, modified with an increased intake of monounsaturated fats and alimentary fibers, on lipid profile and lipid-related cardiovascular risk in 78 normolipidemic and hyperlipidemic renal transplant recipients. Results: Diet led to a significant reduction in total cholesterol levels by 10%, triglycerides by 6.5%, low-density lipoprotein (LDL)-cholesterol by 10.4% and LDL-cholesterol/high-density lipoprotein (HDL)-cholesterol ratio by 10%, whereas HDL-cholesterol levels remained unchanged. Dividing renal transplant recipients into risk classes according to the National Cholesterol Expert Program guidelines and LDL-cholesterol levels, we observed a progressively increasing reduction in total cholesterol and LDL-cholesterol levels among ‘desirable LDL-cholesterol’, ‘borderline high-risk LDL-cholesterol’ and ‘high-risk LDL-cholesterol’ patients, while HDL-cholesterol levels did not change in any group and the LDL-cholesterol/HDL-cholesterol ratio significantly decreased in ‘borderline high-risk LDL-cholesterol’ and in ‘high-risk LDL-cholesterol’ patients (respectively by 6.8%, p < 0.05, and by 21.1%, p < 0.0001). Reduction in triglyceride levels was statistically significant only in subjects with ‘desirable LDL-cholesterol’ (by 12.3%, p < 0.01). Patients in the ‘desirable LDL-cholesterol’ class increased from 28 (35.9% of total patients) before diet to 45 (57.7% of total patients, p < 0.01), while subjects in the ‘high-risk LDL-cholesterol’ class reduced from 24 (30.8% of total patients) to 8 (10.2% of total patients, p < 0.005). Conclusion: These data suggest the possibility of a nutritional hypolipidemic approach in renal transplant recipients, even if normolipidemic. Dietetic treatment determined an inversion in the typical trend of renal transplant recipients, reducing instead of increasing the number of subjects with hypercholesterolemia, permitting the selection of individual candidates for further pharmacological treatment by carefully evaluating risk/benefit costs.
Decrease of Apoptosis Rate in Patients with Renal Transplantation Treated with Mycophenolate Mofetil
Authors: Pardo-Mindán F.J. , Errasti P. , Panizo A. , Sola I. , de Alava E. , Lozano M.D.
Published: April 2003

Background/Aims: Mycophenolate mofetil (MMF) is a powerful immunosuppressant that inhibits the proliferation of lymphocytes by blocking the enzyme inosine monophosphate dehydrogenase. MMF prevents acute graft rejection in organ transplants. The aim of this investigation is to study whether MMF has any influence on apoptosis and proliferation rates of cells other than lymphocytes. Methods: We conducted a retrospective study of renal allograft biopsies taken during the 1st week after transplantation in 25 patients receiving triple therapy with prednisone, ciclosporin and azathioprine 75 mg/day and in 25 patients treated with MMF at a dose of 2 g/day instead of azathioprine, in order to investigate the differences in the proliferation and apoptosis rates of the glomerular, tubular, interstitial and endothelial cells of the kidney. Twelve normal kidneys were used as controls. Conventional histopathological techniques were applied as usual for pathological diagnosis. Proliferative activity was assessed by use of MIB-1 antibody. Sections of formalin-fixed, paraffin-embedded tissue blocks were stained for the presence of apoptotic cells by TUNEL assay. Evaluation of proliferative or apoptotic rates was made by counting the number of positive cells in 10 glomeruli and in 10 transversely cut tubuli in each biopsy. The positive cells in the interstitium were counted in ten high-power fields. Positive cells in the endothelium were scored semiquantitatively from 0 to 3: 0 = none, 1 = isolated cells, 2 = small groups of cells, 3 = most endothelial cells. Mann-Whitney U and chi-square tests were used for intergroup comparisons. Results: All biopsies were normal or had borderline (Banff classification) acute rejection. MIB–1 rates were similar in both groups, without statistical differences (p > 0.05) between them. Significantly lower apoptotic rates were found in the group treated with MMF in tubular epithelium (23.41 ± 8.86 vs. 57.4 ± 13.42; p = 0.021), in glomerular (1.25 ± 0.78 vs. 5.3 ± 1.66; p = 0.027), and interstitial cells (1.58 ± 0.6 vs. 5.8 ± 1.54; p = 0.043). Apoptosis in endothelial cells (p > 0.05) was similar in both groups. Conclusion: We conclude that treatment with MMF of kidney transplant patients does not affect the proliferative rate of cells of the allograft, but decreases the number of apoptotic cells in tubular epithelium.
Size and Charge Selectivity of the Glomerular Filter in Patients with Insulin-Dependent Diabetes mellitus: Urinary Immunoglobulins and Glycosaminoglycans
Authors: Torffvit Ole , Rippe Bengt
Published: April 2003

Background: In diabetic nephropathy, a reduction in negative membrane charge in the glomerular filter, i.e., the number of sulphated groups of glycosaminoglycans, has been argued to lead to increases in excretion of negatively charged molecules, such as albumin and IgG4. However, albuminuria and an increased excretion rate of IgG may also be caused by an increase in radius or number of glomerular large pores. Methods: Timed urinary excretion rates of sulphated glycosaminoglycans, albumin, and IgG2, IgG4, and IgM were analyzed in 94 patients with insulin-dependent diabetes mellitus with different degrees of nephropathy and compared with the excretion rates in 26 control subjects. Sulphated glycosaminoglycans were measured spectrophotometrically after addition of 1,9-dimethylmethylene blue. Albumin and immunoglobulins were measured by immunoassays. Results: With increases in the albumin excretion rate the excretion of IgG2, IgG4, and IgM also increased, in contrast to a decrease in glycosaminoglycans and the ratio between IgG2 and IgG4 (selectivity index). This index decreased from 6.2 to 0.7 (median; p < 0.01). However, with linear regression analysis the excretion rates of albumin and immunoglobulins were not associated with those of glycosaminoglycans. Conclusion: In diabetic nephropathy changes in both large-pore number and in charge selectivity may be pathogenic mechanisms for albuminuria.
Initial Ultrastructural Changes in Pore Size and Anionic Sites of the Glomerular Basement Membrane in Streptozotocin-Induced Diabetic Rats and Their Prevention by Insulin Treatment
Authors: Isogai Sho , Mogami Kosei , Shiina Noriko , Yoshino Gen
Published: April 2003

Background/Aim: The present study was conducted to elucidate the mechanism(s) of the development of early diabetic nephropathy, examining ultrastructural changes employing electron microscopy, especially changes in pore size of the glomerular basement membrane (GBM) of streptozotocin (STZ)-induced diabetics rats. Methods: Urinary albumin excretion rate (UAE), pore size of the lamina densa of the GBM visualized directly by the tissue negative staining method, and number of anionic sites (AS) in the corresponding portion of the lamina rara externa were determined for 6 weeks in diabetic rats without and with insulin treatment. Results: The UAE of the diabetic rats increased with time and was significantly greater than that of the nondiabetic control rats after 4 weeks (p < 0.01), while insulin treatment suppressed the increased UAE of diabetic rats. The median values in both short diameter and long dimension of the pores in the diabetic group were markedly increased at the 2nd week as compared with those in the nondiabetic control rats, whereas no significant change was found in the pore size of the diabetic rats with insulin treatment. Moreover, the number of AS in the GBM of the diabetic rats was significantly (p < 0.001) decreased from the 2nd week onward. Insulin treatment also prevented a decrease in AS number in diabetic rats. Conclusions: It is suggested from these results that an impairment of barrier size selectivity occurs at a very early stage of STZ-induced diabetes in rats, which may enhance the abnormality of the charge-selective properties of the GBM. In addition, insulin treatment may protect this barrier system through normalizing blood glucose control in STZ-diabetic rats.
Influence of Parathyroidectomy and Calcium on Rat Renal Function
Authors: Zaladek Gil F. , Nascimento Gomes G. , Cavanal M.F. , Cesar K.R. , Magaldi A.J.
Published: April 2003

Parathyroid hormone (PTH) has multiple effects on water and electrolyte transport along the nephron. However, the influences of PTH and calcium on the urinary concentration ability are not fully understood. In this study, clearance and microperfusion studies were performed in thyroparathyroidectomized (TPTX) rats either supplemented (TPTX+Ca2+) or not with calcium added to the ingested food as CaCl2 (1.6 g/100 g). Acid-base data and renal functional parameters were measured in TPTX and TPTX+Ca2+ rats. Additional studies were performed in the isolated inner medullary collecting tubules of intact and TPTX rats to evaluate the osmotic permeability of this segment in the presence of 10–6M PTH added to the bath. In these experiments the possible influence of PTH on antidiuretic hormone induced changes of the osmotic permeability in TPTX and TPTX+Ca2+ rats was also investigated. In the TPTX+Ca+ group, the glomerular filtration rate increased significantly when compared to the TPTX group (6.04 ± 0.42 vs. 4.88 ± 0.20 ml·min–1·kg–1; p < 0.05), but the U/P inulin ratio remained lower than control values (30.8 ± 1.48 vs. 54.0 ± 3.5; p < 0.05), which suggests that normal levels of PTH are necessary to maintain the concentrating ability. In a group of TPTX rats, an acute infusion of PTH (0.5 µg·min–1·kg–1) significantly decreased the urinary flow and increased the renal plasma flow, results that agree with the vasomodulator action of this hormone on the renal vasculature. A significant increase in the fractional K+ excretion observed in the TPTX+Ca2+ group as compared with both control and TPTX, groups suggests that the excreted load of Ca2+ may interfere with tubular K+ handling in the absence of PTH. PTH (10–6M) added to the bath of the isolated inner medullary collecting tubules did not change the osmotic permeability, of intact, TPTX, and TPTX+Ca2+ rats. Furthermore, it did not modify the antidiuretic hormone induced changes in the osmotic permeability. These results suggest that this segment of the nephron is PTH insensitive as far as water and ion transport are concerned.
Serum Paraoxonase Activity Changes in Uremic and Kidney-Transplanted Patients
Authors: Paragh György , Asztalos László , Seres Ildikó , Balogh Zoltán , Löcsey Lajos , Kárpáti István , Mátyus János , Katona Evelin , Harangi Mariann , Kakuk György
Published: April 2003

Serum paraoxonase (PON) is a high-density lipoprotein (HDL)-associated hydrolase, which inhibits low-density lipoprotein oxidation. Uremic and kidney-transplanted patients have an increased risk of atherosclerosis, to which an increased lipoprotein oxidation may contribute. The aim of our study was to determine whether the PON activity or phenotype is altered in uremic and kidney-transplanted patients, and to compare the values with those of healthy controls. 117 uremic patients on long-term hemodialysis treatment, 115 renal-transplanted patients, and 110 healthy controls were involved in the study. The PON activity was significantly reduced in the uremic patients compared to controls (PON 101.36±30.12 vs. control 188.05±58.96 U/ml; p < 0.001), while in kidney-transplanted patients the values were almost identical to those of controls (PON 161.5±35.39 U/ml). The different immunosuppressive drug combinations did not influence PON activity. To assess whether the altered PON activity was due to a decrease HDL level, we standardized the enzyme activity for the HDL concentration (PON/HDL ratio). We found that the standardized enzyme activity was lower in the uremic (102.7±54.8) and kidney-transplanted patients (144.5±32.7) when compared to controls (194.5±94.5; p < 0.001). The phenotypic distribution of PON in uremic, renal transplant and control patients are as follows: AA 66.67, 56.48 and 66.67%; AB 31.62, 33.3 and 26.67%; BB 1.71, 10.19 and 6.67%. We conclude that the decreased PON/HDL and PON/apoA-1 ratios may lead to a reduction in the antioxidant capacity of HDL, which might contribute to the accelerated development of atherosclerosis in uremic and kidney-transplanted patients.
Effectiveness of Radiation Therapy in Nephrotic Syndrome Associated with Advanced Lung Cancer
Authors: Shikata Yasushi , Hayashi Yoshiko , Yamazaki Hiroko , Shikata Kenichi , Makino Hirofumi
Published: April 2003

Paraneoplastic nephrotic syndrome is rare, bur occurs mostly in lung cancer. The glomerular lesion usually exhibits membranous nephropathy. Although surgical therapy has been shown to be effective, the treatment of a paraneoplastic nephrotic syndrome has always been a challenge. Currently no standard therapy has been established, if the paraneoplastic nephrotic syndrome is associated with advanced cancer with unresectable lesions. We present 2 cases having paraneoplastic nephrotic syndrome associated with advanced squamous cell carcinoma of the lung. Radiation therapy of the primary tumor effectively caused regression of the paraneoplastic nephrotic syndrome without affecting the renal function. Our results suggest that irradiation can be the first choice in the treatment of nephrotic syndrome, if the primary tumor is unresectable.
Association of a Novel 3-Amino Acid Deletion Mutation of Apolipoprotein E (Apo E Tokyo) with Lipoprotein Glomerulopathy
Authors: Konishi Konosuke , Saruta Takao , Kuramochi Shigeru , Oikawa Shinichi , Saito Takao , Han Hua , Matsunaga Akira , Sasaki Jun
Published: April 2003

Lipoprotein glomerulopathy (LPG) is a newly recognized renal disease characterized by abnormal lipoprotein deposition in the glomeruli, dysbetalipoproteinemia, and a high level of plasma apolipoprotein (apo) E. We identified a novel apo E mutation in a 56-year-old Japanese male with LPG. Although the plasma cholesterol and triglyceride levels were normal, the levels of intermediate-density lipoprotein cholesterol and apo E were elevated to 13 mg/dl (0.336 mmol/l; 4.2±2.9 mg/dl, mean ± SD, in 12 normolipidemic controls) and 9.2 mg/dl, respectively. Biochemical analysis revealed an unusual apo E phenotype (E1/3). Apo E genotyping using DNA digested by a restriction enzyme (HhaI) identified a 66-bp fragment which was not seen with any of the common alleles. Sequence analysis of the amplified genomic DNA fragments showed a 9-bp deletion in exon 4 of the apo E gene resulting in a 3-amino acid deletion (residues 141–143). This novel mutation involves the region of the apo E molecule known to be critically involved in binding to its receptor, and this may well transform the apo E molecule, an inefficient ligand, to its receptor(s). How this mutations causes glomerular damage remains to be determined.
Upregulation of Endothelin A Receptor Sites in the Rabbit Diabetic Kidney: Potential Relevance to the Early Pathogenesis of Diabetic Nephropathy
Authors: Khan Masood A. , Dashwood Mick R. , Mumtaz Faiz H. , Thompson Cecil S. , Mikhailidis Dimitri P. , Morgan Robert J.
Published: April 2003

Background/Aim: Nephropathy is an important complication of diabetes mellitus (DM). The plasma endothelin 1 (ET-1) levels are increased in DM, and ET-1 may cause deleterious effects on renal function. We, therefore, investigated whether changes in ET receptors occur in the DM rabbit kidney. Methods: Nine adult New Zealand White rabbits were injected with alloxan, of which 6 became diabetic; the other 3 acted as alloxan-treated controls. Six age-matched healthy rabbits served as controls. At 6 months, following cervical dislocation, the kidneys were removed, and sections (cortex and medulla) were incubated with ETA and ETB radioligands to produce low- and high-resolution autoradiographs. Immunohistochemical localization of ET-1 immunoreactivity was also performed. Results: There was greater ETA and ETB receptor binding in the control (ETA p = 0.0003; ETB p < 0.0001) and DM (ETA p = 0.001; ETB p < 0.0001) rabbits in the medulla as compared with the cortex. DM kidneys showed a significant increase in ETA, but not ETB, binding in the cortex (p < 0.0001) and in the medulla (p < 0.0001). High-resolution autoradiographs revealed striking [125I]-ET-1 receptor binding predominantly to the glomeruli. Immunohistochemistry revealed dense ET-1 immunoreactivity associated with the renal tubules, but the glomeruli exhibited no staining. Alloxan-treated controls had similar results to age-matched controls. Conclusion: There are regional differences in both ETA and ETB binding in control and DM kidneys. ETA receptor binding sites are increased in the DM kidney (cortex and medulla). ET-1 may act in a paracrine fashion on the glomeruli. These changes may contribute to the pathogenesis of diabetic nephropathy.
Pleural Mesothelioma and Membranous Nephropathy
Authors: Galesic K. , Bozic B. , Heinzl R. , Scukanec-Spoljar M. , Bozikov V.
Published: April 2003

Underlying malignancy has been thought to be responsible for 5–10% of the cases of membranous nephropathy in adults, with the risk being highest in patients over the age of 60 years. Solid tumors such as carcinomas of lung or colon, are most often involved. It is presumed that tumor antigens are deposited in the glomeruli; this is followed by antibody deposition and complement activation, leading to epithelial cell and basement membrane injury and proteinuria due to the associated increase in glomerular permeability. We describe a patient with a resistant nephrotic syndrome and massive proteinuria due to membranous nephropathy associated with pleural mesothelioma.