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Abstract

R.J. Crew, J. Radhakrishnan and G. Appel

Division of Nephrology, Columbia University, New York, NY, USA
The nephrotic syndrome occurs in association with a diverse array of primary and secondary glomerular disorders. Despite the different etiologies, many of the clinical effects are similar. This review focuses on the pathogenesis and treatment of edema formation, hyperlipidemia, and the hypercoagulable state. Major abnormalities of the endocrine system and evidence of erythropoietin deficiency will be reviewed. Finally, non-specific treatments aimed at reducing proteinuria will also be discussed.Correspondence to:
R.J. Crew, M.D. Division of Nephrology Presbyterian Hospital 4-124 Columbia University College of Physicians and Surgeons 622 West 168th Street New York, NY 10032, USA
Email: rc395@columbia.edu

Abstract

R.A. Lafayette and G. Lai

Division of Nephrology, Stanford University Medical Center, Stanford, CA, USA
Aims: The management of patients with chronic kidney disease in outpatient clinics was assessed for the ability to achieve targets of care advocated in clinical practice guidelines. Methods: 272 records of outpatients with increased serum creatinine (³ 1.5 mg/dl for women, ³ 2.0 mg/dl for men) were reviewed for details of their assessment and management. Prevailing data on blood pressure, anemia, bone disease and lipid status as well as therapeutic changes were evaluated. Results: The subjects were aged 64 ± 18 years, serum creatinine 2.6 ± 1.1 mg/dl, and calculated GFR (MDRD formula) 19.2 ± 9.9 ml/min. Median UproV was 1.0 (0.024 – 12.4) g/day. Causes of CKD were diabetes (33.5%), HTN (8.8%), GN (19.5%), and adult PKD (3.3%). Treatment targets were BP < 130/85 mmHg, Hct ³ 36%, serum Ca++ ³ 8.5 mg/dl, serum PO4 < 4.5 mg/dl and cholesterol < 200 mg/dl. Of the patients with abnormal findings, mean values for SBP were 153 ± 17 mmHg, DBP 93 ± 6 mmHg, Hct 31.7 ± 2.9%, Ca++ 8.0 ± 0.7 mg/dl, PO4 5.6 ± 1.0 mg/dl, and cholesterol 236 ± 37 mg/dl. Only a minority of patients with abnormal values had their treatment altered. Furthermore, only 54% of patients with hypertension were treated with either ACEi or ARB therapy. Finally, only 6% of patients with hypercholesterolemia had fasting lipid levels measured. Conclusion: This data suggests that treatment of patients with CKD has improved, but that many opportunities exist to optimize their care.Correspondence to:
R.A. Lafayette, M.D.
Stanford University Medical Center,
Division of Nephrology, M211
Department of Medicine
300 Pasteur Road
Stanford, CA 94305-5114, USA
Email: czar@stanford.edu

Abstract

C.L. Hall, R. Bradley, A. Kerr, R. Attoti and D. Peat

¹Nephrology Unit, Royal United Hospital, Bath, and ²Department of Pathology, Norfolk and Norwich Hospital, Norfolk, United Kingdom
Background: The decision whether to perform renal biopsy on patients with persistent asymptomatic microscopic hematuria (AMH) with and without low-grade proteinuria (LGP) remains controversial as, although often diagnostic, the information gained seldom alters clinical management. Our study investigates the clinical value of renal biopsy in patients with isolated AMH versus those with AMH and LGP. Methods: Between 1996 and 2002, we identified 89 patients with AMH and 46 with AMH and LGP. The patients were asymptomatic, free from systemic illness, had a sterile urine, normal serum creatinine, normal renal and bladder ultrasound, less than 2.5 g proteinuria/day, underwent successful renal biopsy and were followed-up for a mean period of 46 ± 12 months. Results: In patients with isolated AMH, thin basement membrane nephropathy (TBMN) was diagnosed in 43%, IgA nephropathy in 20%, minor abnormalities in 19% and normal biopsies in 18%. In patients with AMH and LGP, IgA nephropathy was diagnosed in 46%, other major nephropathies in 26%, minor abnormalities in 17%, TBMN in 7% and normal biopsies in 4%. At follow-up, 32% of AMH patients and 38% of AMH with LGP patients had a GFR of less than 90 ml/min and 36% and 56%, respectively were hypertensive. Conclusions: The results support the current consensus that routine renal biopsy is not indicated for isolated AMH but suggest that biopsy is indicated for AMH and LGP identifying major and potentially progressive nephropathies in 70% of patients, who should be managed by specialist nephrologists.Correspondence to:
Dr. C.L. Hall
Consultant Nephrologist
The Royal United Hospital
Combe Park, Bath BA1 3NG
Email: clive.hall@ruh-bath.swest.nhs.uk

Abstract

N. Attallah, L. Yassine, J. Musial, J. Yee and K. Fisher

Department of Medicine, Henry Ford Hospital, Detroit, MI, USA
Background: Administration of contrast agents may result in an acute reduction in renal function and occasionally end-stage renal disease. Risk factors for contrast-induced nephropathy (CN) are preexisting renal dysfunction, diabetes and reduced effective arterial volume. Hydration and use of nonionic contrast agents have been reported to ameliorate CN. Reactive oxygen species may have a role in the pathogenesis of CN. Statins decrease free oxygen radicals in animals. We retrospectively tested the hypothesis that administering statins prior to cardiac catheterization decreases the incidence of CN. Methods: A total of 1,002 patients were studied. Patients with a stable baseline serum creatinine (SCr) ³ 1.5 mg/dl who had cardiac catheterization between July 1997 and June 2002, were included in the study. None of the patients were taking statins before admission. 250 patients were started on a statin before the procedure and 752 patients were not. The SCr was followed for 7 days after the procedure looking for an acute decrement in renal function, dialysis requirement and survival. Results: The baseline characteristics, SCr, GFR, amount of intravenous fluids and contrast were similar in both groups. The post cath SCr (2.26 vs 3.1 mg/dl, p = 0.001) was significantly better in the statin group. Length of stay (2.72 vs 3.32 days, p =0.01) and number of patients with acute renal failure (43 (17.2%) vs 168 (22.3%) patients, p = 0.028) were significantly lower in the statin group. Dialysis requirement within 7 days and 28-day survival were similar in both groups. Conclusion: Prophylactic administration of statins along with hydration may be associated with less CN induced by a nonionic, low-osmolality contrast.
Correspondence to:
Dr. N. Attallah
Division of Nephrology and Hypertension
Department of Medicine CFP-5
Henry Ford Hospital
2799 West Grand Blvd.
Detroit, MI 48202, USA
Email: Nattall1@Hfhs.Org

Abstract

P.M. Freese¹, C.T. Svalander², J. Mölne² and G. Nyberg¹

¹Department of Nephrology, and ²Department of Pathology, Sahlgrenska University Hospital, Göteborg, Sweden
Studies of late renal allograft biopsies focus on chronic damage investigated by light microscopy (LM). We evaluated the use of immunohistochemistry (IH) as applied in the routine study of transplant glomerulopathies. Among renal transplants in 1985 – 1997, 129 were identified where a graft biopsy had been obtained 6 months or more after transplantation, studied by LM and IH and the original renal disease was known. IH results were evaluated in relation to glomerular LM findings and the original diagnosis. The risk of graft loss in relation to recurrent and de novo glomerulopathy was evaluated. By LM, 69 biopsies (53%) showed glomerulopathy, mesangial sclerosis only in 26, proliferative changes in 15, membranous in 15 and combined membranous and proliferative in 13. By IH, 46 biopsies (36%) stained positive with IgM and/or complement only and 24 with immune complexes including IgA and/or IgG. Seven biopsies (5.4%) showed glomerular disease by IH in spite of normal LM. Recurrence was diagnosed in 22 grafts; 12 had IgA nephropathy, 3 had SLE, 6 other immune complex nephritides and 1 systemic vasculitis. Twenty-eight biopsies (22%) with proliferative and/or membranous glomerulopathy lacked clear connection to the original renal disorder. More than half of these had deposits of IgM and C3 only. The further graft survival was significantly reduced in the presence of de novo glomerulopathy by LM, relative risk 2.0 (confidence interval 1.1 – 3.8) in a Cox-proportional hazards analysis also including serum creatinine and Banff chronic allograft nephropathy (CAN) grade, p = 0.03. In conclusion, transplant glomerulopathy should be separated from recurrence. De novo glomerulopathy is frequent and ominous.Correspondence to:
Prof. Dr. G. Nyberg
Department of Nephrology
Sahlgrenska University Hospital
S-41345 Göteborg, Sweden
Email: gudrun.nyberg@medic.gu.se

Abstract

R.L. Lins, K.E. Matthys, J.M. Billiouw, M. Dratwa, P. Dupont, N.H. Lameire, P.C. Peeters, J.-C. Stolear, C. Tielemans, B. Maes, G.A. Verpooten J. Ducobu and Y.A. Carpentier

¹ZNA – Jan Palfijn, Merksem, ²Pfizer Global Pharmaceuticals, Medical Department, Brussels, ³Nephrology, OLV Hospital, Aalst, ⁴Nephrology, University Hospital Brugmann, Brussels, ⁵Nephrology, University Hospital Tivoli, La Louvière, ⁶Nephrology, University Hospital, Ghent, ⁷Nephrology, University Hospital VUB, Brussels, ⁸Nephrology, R.H.M.S. Hospital, Tournai, ⁹Nephrology, University Hospital Erasme, Anderlecht, ¹⁰Nephrology, University Hospital Gasthuisberg, Leuven, ¹¹Nephrology-Hypertension, University Hospital UIA, Antwerp, ¹²Endocrinology, University Hospital Tivoli, La Louvière, and ¹³University Hospital Erasme, Anderlecht, Belgium
Background: Patients with end-stage renal disease commonly present with an atherogenic lipid profile characterized by the accumulation of triglyceride-rich, apoprotein B-containing “remnant” lipoproteins, small dense low-density lipoprotein, and low levels of high-density lipoprotein. They are at increased cardiovascular risk and may benefit from drastic lipid-lowering treatment with atorvastatin, a potent, broad-acting lipid regulator. This study aims to assess the effects of atorvastatin on the lipid profile in hemodialysis patients, to determine wether atorvastatin is also effective at lowering lipid levels in this particular high-risk subgroup. Methods: In this randomized, placebo-controlled, double-blind study in hemodialysis patients with hypercholesterolemia (n = 42, mean total cholesterol 243 ± 33 mg/dl (6.3 ± 0.8 mmol/l)), the efficacy of 4-weekly increasing doses of atorvastatin (10 – 40 mg daily) was investigated. Lipids and apoproteins were measured in plasma and isolated lipoprotein fractions. Results: Mean total cholesterol and low-density lipoprotein cholesterol progressively decreased with increasing doses of atorvastatin (total cholesterol –33%, low-density lipoprotein cholesterol –43% after 12 weeks), while high-density lipoprotein cholesterol remained unchanged. Plasma levels of apoprotein B and apoprotein E were also significantly reduced by atorvastatin 10 mg, while up-titration to 20 and 40 mg daily provided additional benefits by lowering triglycerides and apoprotein C-III. At week 12, the fraction of small dense low-density lipoprotein was significantly reduced from 23% – 18%, and apoprotein B-containing intermediate-density lipoproteins were no longer detectable. Conclusion: In conclusion, atorvastatin not only treated hypercholesterolemia but also favorably affected the uremic lipid profile in patients on hemodialysis. Atorvastatin 4-weekly dose escalation up to 40 mg daily was well-tolerated. Further prospective studies are needed to evaluate the impact of this improved lipid profile on morbidity and mortality.
Correspondence to:
Dr. R.L. Lins
ZNA – Jan Palfijn
Lange Bremstraat 70
2170 Merksem
Belgium
Email: robert.lins@village.uunet.be

Abstract

J.T. Kielstein¹, R.H. Böger², S.M. Bode-Böger³, J. Martens-Lobenhoffer³, G. Lonnemann¹, J.C. Frölich⁴, H. Haller¹ and D. Fliser¹

¹Division of Nephrology, Hannover Medical School, Hannover, ²Clinical Pharmacology Unit, Department of Pharmacology, University Hospital Hamburg-Eppendorf, Hamburg, ³Institute of Clinical Pharmacology, Otto von Guericke University, Magdeburg and ⁴Institute of Clinical Pharmacology, Hannover Medical School, Hannover, Germany
Background: Increased blood levels of the endogenous nitric oxide synthase inhibitor asymmetric dimethylarginine (ADMA) predict cardiovascular mortality in patients with end-stage renal disease. Despite its low molecular weight, available information on the impact of hemodialysis (HD) on ADMA plasma levels is controversial. Methods: We assessed plasma concentrations, dialyzer clearance and total amount of ADMA removed in 30 patients with end-stage renal disease during regular HD. In addition, plasma ADMA levels were assessed in 10 patients with acute renal failure treated with extended HD. Results: Regular HD decreased plasma creatinine (from 774 ± 42 to 312 ± 17 mmol/l) and urea (from 24.5 ± 1.5 to 8.4 ± 0.5 mmol/l) concentrations significantly (both p < 0.001), whereas plasma ADMA remained unchanged (4.35 ± 0.19 vs. 4.76 ± 0.24 mmol/l). ADMA clearance was 92 ± 6 ml/min, and the total amount removed in the spent dialysate was 37 ± 4 mmol. The clearances of creatinine (161 ± 3 ml/min) and of urea (173 ± 3 ml/min) were significantly higher. Furthermore, even during extended HD, plasma ADMA concentrations did not decrease significantly (1.73 ± 0.22 vs. 1.63 ± 0.18 mmol/l). Conclusion: In conclusion, dialysance of ADMA is markedly lower than expected from its molecular weight because of significant protein binding of the substance. Since markedly increased ADMA blood concentrations have been linked to cardiovascular complications due to atherosclerosis in patients with ESRD, new strategies should be evaluated to remove this putative uremic toxin.

Correspondence to:
Dr. J.T. Kielstein

Division of Nephrology

Medical School Hannover

Carl-Neuberg-Straße 1

D-30625 Hannover, Germany
Email: Kielstein@yahoo.com

Abstract

T. Ono, H. Goto, K. Morishita, H. Kondo, H. Hirakata and M. Iida

¹Renal Division, Saiseikai Yahata General Hospital, ²Renal Division,
Moji Ekisaikai Hospital, Kitakyushu, and ³Second Department of Internal Medicine, Kyushu University School of Medicine, Fukuoka, Japan
Background: It was reported that pathogenesis of access failure of hemodialysis patients through progressive stenosis was followed by thrombosis. Nonionic contrast media increase platelet degranulation within an angioplasty-damaged vessel by releasing procoagulant molecules, which might contribute to acute thrombosis and restenosis. An adequate level of heparin provides satisfactory thrombin inhibition during routine angioplasty. This study was performed to evaluate the effect of immediate hemodialysis after percutaneous transvenous angioplasty (PTA) to remove nonionic contrast media or other factors while injecting heparin continuously. Methods: From September 9, 1998 – May 15, 2002, successful PTAs were performed in 66 patients with arteriovenous fistula who were not given any inhibitors of platelet aggregation. Hemodialysis was performed in 31 cases immediately after PTA, and in the remainder, hemodialysis was performed the next day. Patients were randomized and fistula patency rates were compared in these 2 groups on March 20, 2004. Results: The patency rates after PTA in patients who were dialyzed immediately, were significantly higher than those who were dialyzed the next day (p = 0.0120). Conclusions: Immediate hemodialysis after PTA is an effective way of increasing the patency of arterio-venous fistula for reasons which are not clear. This observation will need to be corroborated in subsequent studies using a larger sample size.Correspondence to:
Dr. T. Ono
Renal Division, Saiseikai Yahata
General Hospital
5-9-27 Harunomachi, Yahatahigashiku,
Kitakyushu 805-0050, Japan
Email: taka-ono@yf6.so-net.ne.jp

Abstract

H. Yanagida, M. Ikeoka, H. Kuwajima, N. Wada, N. Tabata, K. Sugimoto, M. Okada and T. Takemura

Department of Pediatrics, Kinki University School of Medicine, Osaka-Sayama, Japan
We encountered a 16-year-old boy with Japanese Dent’s disease who exhibited renal insufficiency and an osseous disorder of the spine. Proteinuria first was noted at the age of 2 years. At 13 years, the patient underwent analysis of the CLCN5 gene, which identified missense mutation (I524K) in exon 10. During follow-up, a marked increase in urinary b2-microglobulin was associated with mild deterioration of renal function. At the age of 15 years, hypocalcemia (7.5 mg/dl) accompanied by an increased plasma concentration of alkaline phosphatase was first detected. At that time, plasma concentration of 25(OH)D3 and 1’a25(OH)2D3 were low accompanied by a high plasma parathyroid hormone concentration. A renal biopsy specimen revealed tubulointerstitial alterations including mononuclear cell infiltration, partial fibrosis and focal glomerular sclerosis. Immunofluorescence revealed weak, discontinuous staining of megalin along the brushborder of renal proximal tubules. Western blotting demonstrated decreased urinary excretion of megalin. Thus, clinical manifestations and prognosis may vary in Japanese Dent’s disease. Reduced megalin expression may have disturbed calcium homeostasis, leading to osseous disorder in our patient.Correspondence to:
Dr. T. Takemura
Department of Pediatrics
Kinki University School of Medicine
377-2 Ohno-higashi
Osaka-Sayama, 589-8511, Japan
Email: tsukasa@med.kindai.ac.jp

Abstract

H. Matsukura, A. Higuchi, A. Ieki and T. Miyawaki

¹Department of Pediatrics, Saiseikai Toyama Hospital, ²Higuchi Pediatric Clinic, ³Ieki Obstetrics and Gynecology Hospital, ⁴Department of Pediatrics, Toyama Medical and Pharmaceutical University, Faculty of Medicine, Toyama, Japan
Background: Alport syndrome is a genetically heterogeneous disorder, but most patients showed the X-linked form resulting from mutations in the COL4A5 gene. A few cases of mosaicism in Alport syndrome have been reported. Methods: We describe the case of an 8-year-old boy with mosaicism in Alport syndrome. Punch skin biopsies were obtained from the patient’s mother and monozygotic twin brother. Five biopsy specimens from non-Alport patients were used as controls. Immunohistochemical analysis was performed using rat monoclonal antibodies towards individual collagen IV(NC) domains. Results: Kidney tissue of the patient showed: mosaic expression of a3(IV), a4(IV) and a5(IV) in the glomerular basement membrane (GBM), distal tubular basement membrane (TBM) and Bowman’s capsule; mosaic a6(IV) expression in the Bowman’s capsule and distal TBM; and well-preserved expression of a1(IV) and a2(IV). The patient’s skin exhibited mosaic a5(IV) expression. His mother and monozygotic twin brother disclosed a normal linear staining of a5(IV) in their epidermal basement membranes. This unusual mosaicism of a3(IV), a4(IV), a5(IV) and a6(IV) is consistent with a pattern of female heterozygotes of Alport syndrome. Conclusion: This discordant phenotypic expression of Alport syndrome in monozygotic twins with unaffected parents suggests possible somatic mosaicism in the COL4A5 gene.
Correspondence to:
Dr. H. Matsukura
Department of Pediatrics
Saiseikai Toyama Hospital
33-1 Kusunoki
Toyama, 931-8533, Japan
Email: stingray19659@hotmail.com

Abstract

A.M. Elsharkawy, F. Perrin, C.K.T. Farmer, I.C. Abbs, P. Muir, L.J. Brown, E.M.E. MacMahon and D.J.A. Goldsmith

¹Department of Renal Medicine and ²Department of Infection, Guy?s Hospital, London, and ³Public Health Laboratory, Health Protection Agency South West, Bristol, UK
Cytomegalovirus (CMV) is usually a complication of renal/solid organ or bone marrow transplantation. We describe three cases of severe CMV in the context of vasculitis immunosuppression.Correspondence to:
Dr. D.J.A. Goldsmith Renal Unit Guy?s Hospital 4th Floor, Thomas Guy House, St. Thomas? Street London SE1 9RT, UK
Email: david.goldsmith@gstt.sthames.nhs.uk

Abstract

T. Fehr and H. Rickli

Abstract

H. Inagaki, K. Hamazaki, I. Miho, M. Kuroda and T. Hamazaki

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Volume 62, No. 4/2004(October)