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Abstract

Clinical Nephrology, Vol. 74 – No. 4/2010 (245-257)

Cardiorenal syndrome – a new classification and current evidence on its management

M.S. Ahmed¹, C.F. Wong² and P. Pai¹

¹Royal Liverpool University Hospital, and ²Aintree University Hospital, Liverpool, UK
Patients with chronic kidney disease (CKD) are at high risk for major cardiovascular (CV) morbidity and mortality, especially when they range among the elderly. The co-existence of renal dysfunction is common in patients with chronic heart failure (CHF), and renal failure is among the strongest predictors of mortality in patients with heart failure. Approximately one-third of dialysis patients also suffer from heart failure. The term “cardiorenal syndrome” has been increasingly described in recent literature, as there is growing recognition of the frequent association of combined renal and cardiac dysfunction. The pathophysiology of the cardiorenal syndrome involves interrelated hemodynamic and neurohormonal mechanisms, including the sympathetic nervous system, the renin-angiotensin-aldosterone system, and endothelin and arginine vasopressin system activation. Recently, a new classification of cardiorenal syndrome has been proposed with five subtypes that reflect the pathophysiology, the bidirectional nature of heart and kidney interaction and the time-frame. The management of the cardiorenal syndrome remains a challenge in spite of the advances in medical therapy and novel agents. Novel agents such as B-type natriuretic peptide (BNP) derivative, endothelin antagonist, adenosine antagonist or vasopressin antagonist have been evaluated in randomized controlled trials, and their results are discussed in this review. Mechanical support like hemodialysis and ultrafiltration are found to be useful in acute cardiorenal syndrome. There has been renewed interest in b-blockers in chronic cardiorenal syndrome patients to prevent sudden cardiac death from arrhythmia. In this review, we discuss the evidence behind the definition, pathophysiology, new proposed classification and the various therapeutic measures available for acute cardiorenal syndrome as well as chronic cardiorenal syndrome.Correspondence to:
Dr. M.S. Ahmed
Nephrology Department, Link 6 C
Royal Liverpool University Hospital
Prescot Street, Liverpool L7 3XP, UK
Email: msahmed@doctors.org.uk

Abstract

Clinical Nephrology, Vol. 74 – No. 4/2010 (258-265)

Are tissue samples from two different anatomical areas of the kidney necessary for adequate diagnosis?

J. Gerth¹, M. Busch¹, N. Illner¹, M. Traut¹, H.-J. Gröne² and G. Wolf¹

¹Department of Internal Medicine III, University of Jena, and ²Department of Cellular and Molecular Pathology, German Cancer Research Center, Heidelberg, Germany
Background: An accurate histological diagnosis is of fundamental importance for the therapy and prognosis of many kidney diseases. However, it remains unclear whether a single biopsy is representative of changes in the whole kidney. Methods: To compare the quantity and quality of renal biopsy material taken from two separate areas from one kidney, we prospectively biopsied the renal cortex at the central third and at one of the kidney poles of 103 consecutive 61 native and 42 transplanted kidneys. With two biopsy cores from each kidney we sampled 14.5 ± 8.5 glomeruli/procedure. Results: The length of the biopsy core, the number of glomeruli/core and the markers of chronic renal damage (degree of interstitial fibrosis, proportion of global or segmental scared glomeruli) were not influenced by biopsy location (pole compared with central third locations). Moreover, there was no significant difference in the number of arteries in biopsies obtained from the two different biopsy areas. The percentage between renal cortex and medulla was not influenced by the biopsy area in all kidneys, but transplanted kidney biopsies contained more medulla than specimens from native kidneys. In patients with native kidneys and lower estimated creatinine clearances, there was a nonsignificant trend towards higher variations in the degree of interstitial fibrosis between the two cores, but a coincidence cannot be excluded. There was no significant difference in global sclerotic glomeruli in regard to the biopsy location. Conclusion: We conclude that a renal biopsy composed of two cores from different areas of the kidney provides enough material for histological diagnosis. However, despite the variety of different renal diseases, sampling errors are minimal and obtaining two biopsies from different areas of the kidney does not lead to clinically useful information which would alter the management of patients.Correspondence to:
G. Wolf, MD
Department of Internal Medicine III
University of Jena
Erlanger Allee 101, 07347 Jena, Germany
Email: Gunter.Wolf@med.uni-jena.de

Abstract

Clinical Nephrology, Vol. 74 – No. 4/2010 (266-272)

Poor muscle quality rather than reduced lean body mass is responsible for the lower serum creatinine level in hemodialysis patients with diabetes mellitus

M. Inaba¹, M. Kurajoh¹, S. Okuno², Y. Imanishi¹, S. Yamada¹, K. Mori¹, E. Ishimura¹, T. Yamakawa² and Y. Nishizawa¹

¹Department of Metabolism, Endocrinology and Molecular Medicine, Osaka City University Graduate School of Medicine, Osaka, and ²Shirasagi Hospital, Osaka, Japan
Background: The serum creatinine level is significantly lower in well-nourished hemodialysis patients with diabetes mellitus (DM) than in their non-DM counterparts, despite the presence of anuria in these patients. The factors associated with this finding have not been determined. Patients and methods: We evaluated the association of serum creatinine with handgrip strength (HGS) and lean body mass index (LMI) in a cross-sectional study of 102 DM and 208 non-DM hemodialysis patients to determine if poorer muscle quality in DM patients could explain the reduced level of serum creatinine. All the DM patients were well-nourished. Grip dynamometry and dual-energy X-ray absorptiometry (DXA) were used to measure HGS and LMI, respectively. Results: The DM patients had a significantly lower serum creatinine level and HGS compared to the non-DM patients, but whole-body LMI and LMI of the upper limbs did not differ between the two groups of patients. The DM patients had significantly lower serum creatinine/whole-body LMI, serum creatinine/arm LMI, HGS/whole-body LMI, and HGS/arm LMI ratios. The serum creatinine level was significantly correlated with HGS and with whole-body and upper limb LMI in both groups of patients. However, regression analyses of LMI with serum creatinine and HGS gave significantly shallower slopes for the DM patients compared to the non-DM patients. Conclusion: This suggests that the muscle strength generated per unit of muscle mass, which is reflected well by the serum creatinine level, is significantly reduced in DM hemodialysis patients. Therefore, our results show that the significantly lower serum creatinine levels in DM hemodialysis patients compared to non-DM hemodialysis patients may be explained by poor muscle quality rather than by reduced muscle mass or malnutrition.Correspondence to:
M. Inaba, MD, PhD
Department of Metabolism, Endocrinology and Molecular Medicine
Osaka City
University Graduate School of Medicine
1-4-3, Asahi-machi Abeno
Osaka 545-8585 Japan
Email: inaba-m@med-osaka-cu-ac.jp

Abstract

Clinical Nephrology, Vol. 74 – No. 4/2010 (273-281)

Increased monocyte adhesion-promoting capacity of plasma in end-stage renal disease – response to antioxidant therapy

H. Moradi¹, S. Ganji², V. Kamanna², M.V. Pahl¹ and N.D. Vaziri¹

¹Division of Nephrology and Hypertension, University of California, Irvine, CA, and ²Atherosclerosis Research Center, Department of Veterans Affairs Healthcare System, Long Beach, CA, USA
End-stage renal disease (ESRD) causes accelerated atherosclerosis which is mediated by oxidative stress and inflammation. Activation and infiltration of monocytes represent the critical steps in atherogenesis which is advanced by oxidized LDL and inhibited by HDL. Via its main apolipoprotein (apoA-I) and constituent enzymes (paraoxonase; glutathione peroxidase (GPX), LCAT) HDL exerts potent antioxidant/anti-inflammatory functions. We have found marked reduction of HDL antioxidant/anti-inflammatory and heightened LDL pro-oxidant/pro-inflammatory activities in ESRD patients. Given the inseparable link between oxidative stress and inflammation, we tested the hypothesis that antioxidant therapy may improve anti-inflammatory (monocyte adhesion-promoting capacity) properties of plasma in ESRD patients. Methods: We studied 20 hemodialysis patients who after a 4-week wash-out period were treated with a potent antioxidant cocktail (vitamin (v) E, 800 IU; vC, 250 mg; vB₆, 100 mg; vB₁₂, 250 µg and folic acid 10 mg daily) for 8 weeks. Twelve healthy volunteers served as control. Pre-dialysis plasma samples were obtained at the onset and conclusion of the study. Markers of oxidative stress and inflammation, apoA-I, HDL-associated enzymes and monocyte adhesion assay were measured using cultured aortic endothelial cells. Results: ESRD patients exhibited reduced plasma level of apoA-1 and antioxidant enzymes, elevated markers of oxidative stress and inflammation and heightened monocyte adhesion-promoting capacity. Antioxidant therapy failed to improve these abnormalities. Conclusions: High doses of antioxidant vitamins fail to improve oxidative stress, inflammation or plasma monocyte adhesion-promoting capacity in ESRD patients. Thus, high doses of vitamins beyond the routinely-prescribed supplements do not appear to be beneficial in this patient population.Correspondence to:
N.D. Vaziri, MD, MACP
Division of Nephrology and Hypertension
UCI Medical Center
101 The City Drive, Building 53, Room 125
Orange, CA 92868, USA
Email: ndvaziri@uci.edu

Abstract

Clinical Nephrology, Vol. 74 – No. 4/2010 (282-287)

Ezetimibe decreases serum amyloid A levels in HDL3 in hemodialysis patients

T. Hirano¹, K. Nohtomi¹, N. Nakanishi¹, T. Watanabe², T. Hyodo³ and T. Taira³

¹Department of Diabetes, Metabolism and Endocrinology, ²Department of Biochemistry, Showa University School of Medicine, Tokyo, and ³Department of Nephrology, Yokohama Daiichi Hospital, Japan
Aim: The aim of this study was to investigate the effects of ezetimibe on high-density lipoprotein (HDL) subspecies and serum amyloid A (SAA), an apolipoprotein mainly bound and transported by HDL particles, in patients with end-stage renal disease (ERSD), a condition typically characterized by high SAA- and low HDL-cholesterol (C ) levels. Methods: 26 ERSD patients receiving hemodialysis (HD) were given ezetimibe (10 mg/d) for 6 – 8 weeks. HDL3 was separated from serum by a single precipitation method established by our group. HDL2 was estimated by subtracting HDL3 from total HDL. Serum amyloid A (SAA) was measured by the ELISA method. Results: Ezetimibe significantly reduced remnant-like particle (RLP)-C, low-density lipoprotein (LDL)-C, and apolipoprotein (apo) B without affecting triglyceride, HDL-C and LCAT activities. HDL2-C levels were lower and HDL3-C was substantially lower in the HD patients than in the controls. Ezetimibe increased HDL2-apoAI but decreased HDL3-apoAI without affecting serum apoAI or AII. HDL-SAA was 5-fold higher in the HD patients than in the controls (56 ± 49 vs. 12 ± 9 µg/ml). Ezetimibe decreased HDL-SAA by 43 % (to 32 ± 36 µg/ml), and this inhibitory effect was exclusively attributable to a 72% reduction in HDL3-SAA in response to the ezetimibe treatment. The reduction of HDL3-SAA was significantly associated with increased HDL2-apo AI and reduced HDL3-apo AI. Conclusions: Ezetimibe treatment decreased “inflammatory” (SAA-containing) HDL3, and may thus have restored the anti-atherogenic function of HDL particles in ESRD patients.Correspondence to:
Prof. T. Hirano
Showa University School of Medicine
1-5-8 Hatanodai, Shinagawa-ku, 142-8666 Tokyo, Japan
Email: hirano@med.showa-u.ac.jp

Abstract

Clinical Nephrology, Vol. 74 – No. 4/2010 (288-296)

Hydration with sodium bicarbonate for the prevention of contrast-induced nephropathy: a meta-analysis of randomized controlled trials

H. Trivedi¹, R. Nadella¹ and A. Szabo²

¹Division of Nephrology and ²Department of Population Health, Medical College of Wisconsin, Milwaukee, WI, USA
Background: Whether hydration with sodium bicarbonate is beneficial for the prevention of contrast-induced nephropathy is uncertain. Methods: We conducted a meta-analysis of trials to evaluate the benefit of sodium bicarbonate solutions for the prevention of contrast-induced nephropathy. Our pre-specified criteria were; 1) adult subjects; 2) English literature 3) randomized trials of individuals assigned to a bicarbonate-containing intravenous solution versus an alternate solution; 4) an end-point that included the incidence of contrast-induced nephropathy 5) a uniform contrast agent. Trials in which certain additional prophylactic agents were allowed or administered in a non-standardized, non-stratified manner were ineligible. Results: Ten randomized comparisons of sodium bicarbonate versus sodium chloride satisfied study criteria (total n = 1,090). The majority of studies involved subjects undergoing cardiac angiography and a nonionic low osmolar contrast agent was used in most instances. Woolf’s test showed no evidence of heterogeneity (p = 0.10; I² = 39%) and there was no publication bias (p = 0.34). The effect size using the exact Mantel-Haenszel-test revealed an odds ratio (OR) of 0.57 (95% CI: 0.38 – 0.85) for the occurrence of contrast-induced nephropathy with the use of sodium bicarbonate. An analysis restricted to studies that employed hydration without additional prophylactic agents favored sodium bicarbonate to a greater extent (OR 0.33:95% CI: 0.17 – 0.62). However, many trials in this arena may not be considered high-quality studies. Conclusion: Though inference should be tempered by trial quality issues, given lack of heterogeneity or publication bias the summary effect of randomized trials balanced in important characteristics favors hydration with sodium bicarbonate for the prevention of contrast-induced nephropathy.Correspondence to:
H. Trivedi, MD
9200 W. Wisconsin Ave.
Milwaukee, WI 53226, USA
Email: htrivedi@mcw.edu

Abstract

Clinical Nephrology, Vol. 74 – No. 4/2010 (297-302)

High dose urokinase for restoration of patency of occluded permanent central venous catheters in hemodialysis patients

L. Shavit, M. Lifschitz, J. Plaksin, T. Grenader and I. Slotki

Nephrology Unit Shaare Zedek Medical Center, Jerusalem, Israel
Background: Catheter thrombosis is common and results in inadequate dialysis treatment and, frequently, in catheter loss. Since dialysis treatment runs on a strict schedule, occluded catheters need to be restored in a timely and cost effective manner. We present a new shortened protocol of urokinase infusion that allows hemodialysis to be performed within 90 minutes. Methods: To chronic hemodialysis patients, who developed complete catheter occlusion, urokinase was infused simultaneously through both lumens of the catheter (125,000 units to each lumen) over 90 minutes. Technical success was defined as restoring blood pump speed to at least 250 ml/min. We determined the average time from catheter placement to first clot event (primary patency PP), recurrent clot event after urokinase treatment (secondary patency SP), catheter salvage rate and cause for removal. Results: 37 catheters developed total thrombosis and urokinase was used to restore patency one or more times (total 47 treatments). Catheter salvage rate was 97 %. The average time of PP was 152 ± 56 days (7 – 784 days). Nine patients (30%) developed recurrent occlusion and the average time of SP was 64 ± 34 days (2 – 364 days). One catheter was removed because of dysfunction due to thrombosis. Other catheters were removed due to infection, fistula maturation or fell out spontaneously. Hemodialysis was performed immediately after treatment with blood speed of 250 ml/min in all patients. Conclusion: Our protocol is highly effective, short, and allows to restore patency of totally occluded central venous catheters with minimal disruption of the dialysis session.Correspondence to:
L. Shavit, MD
Nephrology Unit
Shaare Zedek Medical Center
PO Box 3235, Jerusalem 91031, Israel
Email: lshavit@szmc.org.il

Abstract

Clinical Nephrology, Vol. 74 – No. 4/2010 (303-307)

The successful treatment of rapidly progressive idiopathic membranoproliferative glomerulo-nephritis Type 1 in a 4-year-old male pediatric patient

S. Fujinaga¹, Y. Ohtomo², D. Hirano¹, N. Nishizaki¹, T. Someya³, Y. Ohtsuka³, K. Kaneko⁴ and T. Shimizu³

¹Division of Nephrology, Saitama Children’s Medical Center, Saitama, ²Department of Pediatrics, Juntendo Nerima Hospital, ³Department of Pediatrics, Juntendo University School of Medicine, Tokyo, and ⁴Department of Pediatrics, Kansai Medical University, Osaka, Japan
A multivariate analysis [4] revealed that the presence of crescent formation on initial biopsy irrespective of type of membranoproliferative glomerulonephritis (MPGN) was independently associated not only with end-stage renal disease but also with post-transplantation recurrence. In this study, we reported on a 4-year-old male pediatric patient requiring hemodialysis due to rapidly progressive idiopathic MPGN Type 1 with severe nephrotic syndrome and extensive cellular crescent formation on initial biopsy. The patient had been treated intravenously (i.v.) with 9 pulses of methylprednisolone, followed by daily prednisolone, resulting in the withdrawal of dialysis within 1 month. However, since active lesions in the second renal biopsy such as cellular crescents still remained and nephrotic range proteinuria had persisted for more than 2 months, the patient received additional 3 i.v. pulses of methylprednisolone, followed by combinations of alternate-day prednisolone, mizoribine, dipyridamole and warfarin, which lead to complete remission in a short-period of time. The patient has been off the combination therapy for 10 months because the third biopsy prior to the termination of this regimen showed decreased inflammatory activity. There is currently no established protocol for children with crescentic MPGN due to a rarity of its clinicopathological presentation. This case report indicates that early treatment with multiple pulses of methylprednisolone followed by the short-term combination therapy may be of benefit for children with rapidly progressive idiopathic MPGN Type 1, even when both diffuse crescentic changes and nephrotic syndrome are present at onset.Correspondence to:
S. Fujinaga, MD, PhD
Division of Nephrology
Saitama Children’s Medical Center
2100 Magome, Iwatsuki-ku
Saitama-city Saitama 339 8551, Japan
Email: f_shuich@d2.dion.ne.jp

Abstract

Clinical Nephrology, Vol. 74 – No. 4/2010 (308-310)

Rituximab for steroid-dependent nephrotic syndrome

A. Beco, I. Castro-Ferreira, L. Coentrao, R. Neto, S. Sampaio and M. Pestana

Nephrology Research and Development Unit, Faculty of Medicine, University of Porto and Hospital de S. Joao EPE, Alameda Prof. Hernani Monteiro, Porto, Portugal
Minimal change disease (MCD) is characterized by marked sensitivity to glucocorticoid therapy. However, in 40 – 50% of all cases the disease presents with frequent relapses and needs repeated courses of steroids as well as additional immunosuppressive therapy including azathioprine, cyclophosphamide or cyclosporine. Because such regimens are associated with significant toxicity, the therapeutic challenge of this disease is to identify the treatment with the highest probability of producing a sustained remission with the lowest risk of toxicity. There is increasing evidence that rituximab may play an important role in the treatment of idiopathic nephrotic syndrome. Here, we present an adult patient with steroid-sensitive but high-dose steroid-dependent MCD beginning in childhood with a heavy history of multiple immunosuppressive therapy that was brought into 1 year sustained remission of proteinuria with two infusions of rituximab (375 mg/m²).Correspondence to:
A. Beco
Nephrology Research and Development Unit
Faculty of Medicine
University of Porto and Hospital de S. Joao EPE
Alameda Prof. Hernani Monteiro
4202-451, Porto, Portugal
Email: coentrao@med.up.pt

Abstract

Clinical Nephrology, Vol. 74 – No. 4/2010 (311-314)

Nonsecretory multiple myeloma – a rare case of acute renal failure

K.N. Adamidis¹, E.E. Charitaki¹, C. Christodoulidou¹, A. Tasidou² and V. Hadjiconstantinou¹

¹Department of Nephrology, and ²Department of Hemopathology, Evangelismos General Hospital, Athens, Greece
Multiple myeloma (MM) is a plasma cell dyscrasia accounting for 10% of all hematologic malignancies. Diagnosis is based on histologic, serologic and radiographic features. The nephrotoxic manifestations of immunoglobulin light chain overproduction are the most common cause of renal function impairment. The most frequent renal lesion is “cast nephropathy” and results from immunoglobulin light chain nephrotoxicity. MM very rarely produces diffuse bilateral renal infiltration. We report the interesting case of a patient with non-secretory myeloma, who presented with acute renal failure and increased kidney size due to massive renal infiltration by plasma cells. Pulse steroid therapy lead to rapid renal function improvement and reduction in kidney size. Renal failure is a frequent manifestation of MM, which can affect kidneys in several ways. MM should be included in the differential diagnosis of every case of unexplained renal failure, especially in the elderly, even in the absence of an M spike in serum and urine electrophoresis.Correspondence to:
K.N. Adamidis, MD
Department of Nephrology
“Evangelismos” General Hospital
45 – 47 Ipsilantou str.
106 76, Athens, Greece
Email: kostasadamidis@yahoo.gr

Abstract

Clinical Nephrology, Vol. 74 – No. 4/2010 (315-318)

Classic polyarteritis nodosa presenting with rapidly progressive renal insufficiency

Y. Oe¹, I. Nakaya¹, M. Yahata¹, T. Sakuma² and J. Soma¹

Departments of ¹Nephrology and ²Pathology, Iwate Prefectural Central Hospital, Morioka, Japan
Rapidly progressive renal insufficiency is rare in patients with classic polyarteritis nodosa (cPAN). We describe two cases of cPAN who presented with rapid and progressive deterioration of renal function. Renal biopsies showed severe necrotizing vasculitis in medium-sized arteries but no changes in glomeruli. Combination therapy of corticosteroid and cyclophosphamide resulted in marked improvement of clinical symptoms, amelioration of renal function and lack of subsequent relapse of vasculitis. These findings suggest good prognosis of patients with cPAN who show rapid and progressive deterioration of renal function who respond to immunosuppressive therapy.Correspondence to:
Y. Oe, MD
Department of Nephrology
Iwate Prefectural Central Hospital
1-4-1 Ueda, Morioka, 020-0066, Japan
Email: oaugpkd40@hotmail.com

Abstract

Clinical Nephrology, Vol. 74 – No. 4/2010 (319-322)

Prolonged hemodialysis for acute kidney injury in myeloma patients

W. Hanf¹, C. Guillaume², A. Jolivot¹, C. Chapuis-Cellier³, F. Guebre-Egziabher¹, A. Fontana⁴, D. Fouque¹ and L. Juillard¹,⁵

¹Nephrology, ²Intensive Care, ³Biochemistry and ⁴Rhumatology Departments, Hôpital E Herriot, Hospices Civils de Lyon, and ⁵Université de Lyon, Lyon, France
Objective: Cast nephropathy, due to free light chain (FLC) toxicity, is the main cause of acute kidney injury in multiple myeloma, with about 10% of patients requiring dialysis. In these patients, in addition to chemotherapy that prevents FLC production, daily hemodialysis using high cutoff or adsorptive membranes, showed promising results by decreasing quickly toxic serum FLC concentrations. Case history: We report here the case of 2 patients presenting with acute kidney injury and high FLC serum concentration and M-components one with IgG Kappa and the other with IgD lambda. Both were treated with bortezomib and dexamethasone and received a 24-h continuous hemodialysis using a high and sharp cutoff (around 35,000 Daltons) polysulfone membrane (ultraflux^® HD 1000, Fresenius Medical Care GmbH, Bad Homburg, Germany) with citrate regional anticoagulation using a safe and dedicated device (multi filtrate Ci-Ca^®). Conclusion: Despite similar range of depuration, serum plasma FLC decreased importantly in the patient with the kappa type who recovered but was unchanged in the lambda type patient who remained under maintenance dialysis. Further studies are needed to confirm this new approach therapy.Correspondence to:
L. Juillard, MD, PhD
Nephrology Department
E. Herriot Hospital
5 place d’Arsonval
69437 Lyon cedex 03, France
Email: Laurent.juillard@chu-lyon.fr

Abstract

N-acetylcysteine in critically ill patients undergoing contrast-enhanced computed tomography: a randomized trial

K.E.A. Burns, F. Priestap and C. Martin

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Volume 74, No. 4/2010(October)