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Abstract

S. Shaldon

Abstract

B.I. Shand, J.G. Lewis, P.A. Elder and M. Agarwal

Abstract

R.D. Toto

Department of Medicine, University of Texas Southwestern Medical Center Dallas, Texas, USA
Important advances in our understanding of the mechanisms and treatment of hypertension in patients at risk for renal disease and those with overt renal disease are taking place. Thus, new data suggest that hyperfiltration may be an important antecedent to the development of kidney disease in hypertensive African-Americans. Also new studies provide evidence for differential responses of endothelial function and sympathetic nerve traffic to ACE inhibitors versus dihydropyridine calcium channel blockers in hypertensives with and without overt renal disease. Important new studies also show that in proteinuric subjects ACE inhibitor treatment is superior to non-ACE treatment at reducing proteinuria and the risk of developing ESRD in non-diabetics with renal disease. In hemodialysis patients, both systolic hypertension and hypotension predict increased mortality in hemodialysis patients. And, identification of factors important in persisting hypertension in patients on hemodialysis provide new insights into improving BP control in this population. The purpose of this review is to highlight the key elements and clinical relevance of these recent studies.

Abstract

M.V. Pahl, C.C. Nast and S.G. Adler

¹Nephrology, University of California, Orange, CA, ²Pathology, Cedars-Sinai Medical Center, Los Angeles, CA, and ³Nephrology, Harbor UCLA, Torrance, CA, USA
Controversy exists regarding the level of proteinuria in patients with nephrosclerosis. Material and methods: We retrospectively examined the clinical parameters of 67 patients with the histologic diagnosis of nephrosclerosis defined as arteriolar hyalinization and/or arterial intimal fibrosis in the absence of other findings in an adequate renal biopsy. Biopsies were performed for clinical indications and were submitted to Cedars-Sinai Pathology Department from January 1994 to March 1999. Results: The mean age and blood pressure (± SD) was 60 ± 17 years, and 139 ± 19/80 ± 12 mmHg. Mean serum creatinine was 2.3 ± 1.3 mg/dl and 24-hour urinary protein excretion was 0.94 ± 0.73 g, 66% had £ 1 g/day, 25% had > 1 but £ 2 g/day, 6% had > 2 g but < 3 g/day and 1 patient had nephrotic range proteinuria. Twelve patients had no history of hypertension. They had a mean blood pressure of 121 ± 8/76 ± 8. Their mean serum creatinine was 1.5 ± 0.6 mg/dl and their mean 24-hour urinary protein excretion was 0.78 ± 0.43 g. Conclusions: Our data do not confirm that of Innes et al. [1993] who reported proteinuria > 1.5 g/day in 40% and nephrotic syndrome in 22% of patients with nephrosclerosis; systemic hypertension may not be a prerequisite for the development of nephrosclerosis.

Abstract

A.J.W. Branten, I.S. Klasen and J.F.M. Wetzels for the Study Group

¹Department of Medicine, Division of Nephrology, ²Department of Clinical Chemistry, University Medical Center Nijmegen, Nijmegen, The Netherlands
Aims: Recently, it was shown that fish oil treatment improved renal survival in patients with IgA nephropathy. The precise mechanisms of this protective effect remained unclear. Omega-3 polyunsaturated fatty acids (PUFAs), important active substances of fish oil, are able to attenuate inflammatory responses. Thus, the renoprotective effects of fish oil may be the result of mitigation of glomerular or tubulo-interstitial inflammation. We hypothesized that such a decrease in glomerular or tubulo-interstitial inflammation could result in an improvement of glomerular permselectivity as reflected by the urinary excretion of IgG, or of tubular reabsorption capacity as reflected by the urinary excretion of low-molecular weight proteins (LMWPs), or a decrease of the excretion of the inflammatory mediators MCP-1 and TNF-a. Methods: Twelve patients with a biopsy-proven IgA nephropathy, a persistent proteinuria of > 0.5 g/24 h, and an impairment of renal function (creatinine clearance 44 ml/min/1.73 m2, range 19 – 72) were treated with fish oil for 6 months. The daily dosage of PUFAs amounted to 3.0 g. Before start of treatment (month 0), at the end of treatment (month 6), and 6 months off treatment (month 12), renal measurements were carried out. Creatinine clearance (ECC) was measured after pretreatment with cimetidine. In timed urine samples albumin, IgG, the LMWPs b2-microglobulin and a1-microglobulin, and both MCP-1 and TNF-a were measured. Results: Six months of fish oil treatment had no effect on creatinine clearance (44 ml/min/1.73 m2 vs 42 ml/min/1.73 m2), the urinary excretion of albumin (1,594 ± 284 vs 1,370 ± 337 mg/min), IgG (84 ± 16 vs 82 ± 20 mg/min), b2-microglobulin (medians: 1.0 vs 0.8 mg/min), a1-microglobulin (38 ± 9 vs 53 ± 15 mg/min), MCP-1 (medians: 720 vs 782 pg/min), or TNF-a (medians: 31 vs 27 pg/min). Mean arterial pressure gradually decreased from 102 ± 4 to 96 ± 4 mmHg at the end of the treatment (n.s.), however, the lowest value was observed after fish oil had been stopped for 6 months (93 ± 3 mmHg, p < 0.05). Changes in the excretion of the urinary proteins during the 12-month study period were correlated to changes in blood pressure (r = 0.57, p < 0.01), independent of fish oil treatment. The course of the disease over the 12-month study period in our fish oil-treated patients was comparable to that of an untreated control group. Conclusions: Fish oil treatment in patients with IgA nephropathy, renal insufficiency and proteinuria did not affect the excretion of low- or high-molecular weight proteins, MCP-1 or TNF-a. Our data do not provide arguments for beneficial effects of fish oil treatment on glomerular permselectivity of tubulo-interstitial inflammation.

Abstract

O.F. Thomsen and J. Ladefoged

Department of Nephrology P and Department of Pathology, Rigshospitalet, Copenhagen, Denmark
Aims: The relation between histological and clinical parameters were studied in 54 consecutive patients with acute interstitial nephritis or pyelonephritis without primary glomerular disorders, in all of whom percutaneous renal core biopsy had been performed. Patients and methods: Based on clinical criteria and without detailed knowledge of the appearance of the biopsy, the material was divided into 4 main groups: patients with septic and/or tubulotoxic conditions, hypersensitivity reactions (eosinophilic nephritis), ascending infections and other specified conditions. Results: The overall correlation between the histological and the clinical diagnoses was good, but there were large overlaps between the histological findings in 3 of the groups, making classification of individual cases difficult. The histological and paraclinical findings were poorly correlated. Histologically, ascending infections were characterized by the presence of leukocyte casts and an increased number of neutrophilic granulocytes. Conclusion: The material justifies the present rough classification of the conditions mentioned above. By kidney biopsy, the interstitial conditions can be separated from glomerular and other conditions, but the biopsy offers little information about the clinical severity or the prognosis.

Abstract

B.M. Curtis, B.J. Barrett, K. Jindal, O. Djurdjev and A. Levin for CREDA (Canadian Renal Disease Alliance): P. Barre, K. Bernstein, P. Blake, E. Carlisle, P. Cartier, C. Clase, B. Culleton, C. Deziel, S. Donnelly, J. Ethier, A. Fine, G. Ganz, M. Goldstein

¹Division of Nephrology and ²Clinical Epidemiology Unit, Memorial University of Newfoundland, ³Division of Nephrology, Dalhousie University, ⁴Center for Health Evaluation and Outcome Sciences (CHEOS), and ⁵Division of Nephrology, St. Paul's Hospital, Univ
Aims: The current growth in end-stage kidney disease populations has led to increased efforts to understand the impact of status at dialysis initiation on long-term outcomes. Our main objective was to improve the understanding of current Canadian nephrology practice between October 1998 and December 1999. Methods: Fifteen nephrology centers in 7 provinces participated in a prospective data collection survey. The main outcome of interest was the clinical status at dialysis initiation determined by: residual kidney function, preparedness for chronic dialysis as measured by presence or absence of permanent peritoneal or hemodialysis access, hemoglobin and serum albumin. Uremic symptoms at dialysis initiation were also recorded, however, in some cases these symptom data were obtained retrospectively. Results: Data on 251 patients during 1-month periods were collected. Patients commenced dialysis at mean calculated creatinine clearance levels of ~ 10 ml/min, with an average of 3 symptoms. 35% of patients starting dialysis had been known to nephrologists for less than 3 months. These patients are more likely to commence without permanent access and with lower hemoglobin and albumin levels. Even of those known to nephrologists, only 66% had permanent access in place. Conclusions: Patients commencing dialysis in Canada appear to be doing so in relative concordance with published guidelines with respect to timing of initiation. Despite an increased awareness of kidney disease, a substantial number of patients continues to commence dialysis without previous care by a nephrologist. Of those who are seen by nephrologists, clinical and laboratory parameters are sub-optimal according to current guidelines. This survey serves as an important baseline for future comparisons after the implementation of educational strategies for referring physicians and nephrologists.

Abstract

S. Disthabanchong, E.A. González and K.J. Martin

Division of Nephrology, Saint Louis University, St. Louis, Missouri, USA
Osteitis fibrosa, a part of the spectrum of renal osteodystrophy, is characterized by high bone turnover as a result of high circulating levels of parathyroid hormone (PTH). It is well accepted that the bone resorptive effects of PTH occur, at least in part, by inducing osteoblasts to secrete cytokines that stimulate both differentiation and activation of osteoclasts. One such cytokine, interleukin 6 (IL-6), exerts its actions via the IL-6 receptor (IL-6R), which has a and b subunits. The a subunit binds IL-6 and exists in both membrane bound and soluble forms which can interact with the signal transducing components of the receptor or b subunits and result in the same biological effect. Abnormalities in the IL-6 system have the potential to affect bone turnover and to modulate the effects of PTH. In this regard, we examined the levels of circulating soluble IL-6 receptor (sIL-6R) and plasma intact PTH in 27 patients on hemodialysis, of whom 15 were on therapy with vitamin D compounds and 12 were vitamin D naïve. The results were compared to values obtained from 9 healthy controls. Blood samples were obtained pre-dialysis and sIL-6R levels were determined using a commercially available enzyme immunoassay, which measures biologically active sIL-6R. In patients on chronic hemodialysis, plasma levels of sIL-6R were 123.4 ± 11.01 ng/ml. In healthy controls, the levels were 99.61 ± 11.52 ng/ml, values not significantly different from those found in dialysis patients. PTH values ranged from 7 – 1,709 pg/ml in patients on hemodialysis; however, there was no correlation between intact PTH levels and the levels of sIL-6R. Similarly, vitamin D therapy did not influence the levels of sIL-6R. These data indicate that using an assay which is specific for biologically active sIL-6R, the levels of this receptor in patients on hemodialysis are similar to those found in normal individuals and neither the levels of PTH nor vitamin D therapy alter this aspect of IL-6 action.

Abstract

A. Kato, H. Yasuda, A. Togawa, T. Yamamoto, K. Yonemura, T. Maruyama, Y. Maruyama and A. Hishida

First Department of ¹Medicine and ²Dialysis Unit, Hamamatsu University School of Medicine, ³Maruyama Hospital, Hamamatsu and ⁴Shizuoka Cancer Center Hospital, Nagaizumi-cho, Shizuoka, Japan
Background: The prevalence of anti-hepatitis virus C (HCV) antibody is much higher in hemodialysis (HD) patients than in the normal population. Recently, blood des-g-carboxy prothrombin (PIVKA-II) has been demonstrated as a sensitive marker for the early detection of hepatocellular carcinoma (HCC). In this study, we measured blood PIVKA-II in HD patients positive for anti-HCV antibody or hepatitis B virus surface (HBs) antigen to examine if HD therapy may affect the measurement of PIVKA-II. Patients and methods: Ninety-four stable HD patients who had anti-HCV antibodies (n = 86) or HBs antigen (n = 8) without any evidence of HCC were enrolled in the study (age: 60 ± 11 years, duration of HD: 17 ± 10 years, male/female = 63/31). Five patients had liver cirrhosis and another 5 patients received warfarin treatment. We simultaneously measured serum PIVKA-II and a-fetoprotein (AFP), and compared the association between these markers and HCV RNA titer and laboratory parameters. Results: Serum PIVKA-II became positive (³ 40 mAU/ml) in only 5.6% (5/89) of patients without warfarin administration, ranging from 47 to 71 mAU/ml. Seventy out of 89 patients (78.7%) were below 20 mAU/ml. Serum PIVKA-II did not correlate with biochemical parameters including HCV RNA, while serum AFP was significantly correlated with serum AST (r = 0.21, p < 0.05), g-GTP (r = 0.21, p < 0.01) and platelet counts (r = –0.29, p < 0.01), respectively. In contrast, 5 patients receiving warfarin had an extremely high PIVKA-II value ranging from 1,930 to 19,900 mAU/ml. PIVKA-II was significantly and inversely correlated with the thrombotest value (r = –0.72, p = 0.01). Conclusion: The positivity of blood PIVKA-II in HD patients with hepatitis viremia was identical to that in patients without renal failure. Warfarin treatment dramatically increased serum PIVKA-II more than 1,000 mAU/ml. These findings suggested that HD treatment itself did not affect the measurement of PIVKA-II, but vitamin K deficiency can readily influence the PIVKA-II level in dialysis patients.

Abstract

M. Jadoul and P. Goubau

Departments of ¹Nephrology and ²Virology, Cliniques Universitaires St. Luc, Université catholique de Louvain, Brussels, Belgium
Background: The success rate of anti-hepatitis B virus (HBV) immunization is known from the early 80s to be markedly lower in hemodialysis (HD) patients (around 60%) than in non-uremics (over 90%). It is also known to be inversely correlated with age in non-uremics, but the rate of successful immunization in the currently prevalent elderly HD patients is unknown. Methods: We therefore reviewed our experience in patients vaccinated soon after starting HD in 1997 – 2000. A recombinant vaccine (Engerix 20 mg) was administered monthly in the deltoid muscle until anti-HBs titer was ³ 100 IU/l or up to 10 doses or death, whichever occurred first. Conventional serological tests for anti-HBc, anti-HBs and HBs Ag were performed 5, 6, 9 and 12 months after the first dose of vaccine. Results: Ninety-six patients started HD during this period. Sixty-five of them were excluded for the following reasons: evidence of past HBV infection (n = 20, 21%), previous anti-HBV vaccination (n = 13, 14%), rapid transfer to another HD unit (n = 30, 31%), early death (n = 2, 2%). In the remaining 31 patients, with a median age of 73 (range 35 – 95) years, the vaccination schedule induced seroconversion in 13/31 (42%) and 16/23 (70%) after 5 and 12 months, respectively. The seroconversion rate after 12 months was 3/3 (100%), 9/12 (75%) and 4/8 (50%) in patients aged < 60 years, 60 – 75 years and > 75 years, respectively. Patients with seroconversion were younger (66 ± 14 years) than those without seroconversion (76 ± 9 years) (p = 0.048, unpaired t-test). In the whole cohort, evidence of past HBV infection was more common in patients originating from outside Northern Europe (mainly Africa or Mediterranean countries) (14/26, 54%) than in patients from Northern Europe (6/70, 9%) (p < 0.001, Fisher exact test). Conclusion: Up to 50% of elderly (> 75 years) HD patients can be successfully immunized with a reinforced anti-HBV vaccination schedule, a proportion still much lower than in younger HD patients. The ultimate decision to vaccinate elderly HD patients more or less intensively, or not at all, should depend on the local epidemiology of HBV infection and the individual risk of acquiring HBV (e.g. through holiday dialysis in high prevalence countries). Before vaccinating, serological screening of patients originating from countries with high HBV prevalence is recommended.

Abstract

M. Rüster, K. Abendroth, G. Lehmann and G. Stein

Department of Internal Medicine IV, University of Jena, Germany
In this study, the sensitivity of the aurine tricarboxylic acid (ATA) and acid solochrome azurine (ASA) stain for aluminum were compared under special consideration of the relationship to bone histology in renal osteodystrophy. Al deposition in iliac crest bone biopsies taken from 78 patients with chronic renal failure (CRF) was assessed histochemically using the ATA and ASA stain; the Al accumulation was correlated with bone histology and histomorphometry. Significantly more Al was detectable with the ASA method on trabecular bone surfaces and cement lines (18 ± 20% vs 4 ± 12% on surfaces; 13 ± 18% vs 0.4 ± 1.3% on cement lines). In 31 cases in which ATA yielded negative results, ASA in contrast indicated Al deposits on up to 20% of the trabecular bone surface. The specimens with more Al on the trabecular bone surface had a significantly higher osteoid volume and osteoid surface. With ATA, these differences were observed at a staining of ³ 10% of the trabecular surface, with ASA at a staining of ³ 40% of the trabecular surface. Therefore, it seems to be possible to detect a very low Al deposition, without any Al-induced changes in bone morphology or signs of Al toxicity in the bone using the ASA method. By contrast, a positive ATA stain is mainly found in biopsies with typical signs of Al-induced changes of histomorphometric bone parameters. We, therefore, recommend the routine use of the ASA stain to detect Al deposition in bone.

Abstract

T. Ohta, T. Sakano, T. Ogawa,J. Kato, Y. Awaya, H. Kihara and Y. Kinoshita

¹Department of Pediatrics, and ²Internal Medicine, Hiroshima Prefectural Hospital, Hiroshima, Japan
A previously healthy 16-year-old boy developed acute renal failure following a track race at a local athletic meeting. Several hours after the run, he expressed pain in the loins with nausea and vomiting. After 3 sessions of hemodialysis, he was referred to our hospital. On admission, serum creatinine was elevated to 2.3 mg/dl without an increase in serum uric acid level. After recovery from acute renal failure (ARF), hypouricemia (0.7 mg/dl) became evident in the patient. One year later, he suffered from ARF after a track race with the highest creatinine levels of 1.1 mg/dl. In order to clarify the cause and prognosis of ARF with renal hypouricemia, we summarized the clinical features in 18 patients previously described and our patient. Serum uric acid levels after recovery from ARF were below 1.0 mg/dl in all patients. Renal biopsy in 9 patients showed acute tubular necrosis in 8 patients and uric acid nephropathy in 1. The short-term prognosis of these patients seemed good, although 5 patients needed to undergo hemodialysis in their ARF courses. However, the recurrence of ARF episodes occurred in 6 patients (31.6%) including our patient, indicating that prevention of ARF might be necessary in these patients. More information is required to establish guidance for prevention of ARF.

Abstract

H. Fukasawa, A. Kato, T. Fujimoto, H. Suzuki, Y. Fujigaki, T. Yamamoto, A. Endoh, K. Yonemura and A. Hishida

¹First Department of Medicine, ²Department of Pediatrics and ³Hemodialysis Unit, Hamamatsu University School of Medicine, Hamamatsu, Japan
Panhypopituitarism manifests various symptoms including growth failure, hypothyroidism, adrenal insufficiency and hypogonadism. Dwarfism is an important problem in children with this condition, and long-term treatment with recombinant human growth hormone (GH) is usually required. We report a 24-year-old man with panhypopituitarism complicated by focal segmental glomerulosclerosis (FSGS). The patient had been treated with GH for hypopituitary dwarfism from 3 years of age. Proteinuria was initially noticed at 15 years of age and persisted despite cessation of GH supplementation at 18 years of age. A renal biopsy specimen showed glomerular hypertrophy and limited glomerulosclerosis, compatible with FSGS. To our knowledge, this is the first reported case of panhypopituitarism complicated by FSGS. Our case suggests that GH treatment for dwarfism may induce irreversible glomerular disease.

Abstract

S. Ahmed, A. Karim, M.M. Hoffman, T.A. Bhuiya and J. Mattana

Abstract

N. Bassilios, A. Restoux, F. Vincent, E. Rondeau and J.-D. Sraer

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Volume 58, No. 4/2002(October)