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Abstract

P. Rosenbaum, S.G.A. Gimeno, A. Sanudo, L.J. Franco and S.R.G. Ferreira for the Japanese-Brazilian Diabetes Study Group

¹Endocrinology Division, Internal Medicine Department, ²Preventive Medicine Department, ³Epidemiology Division, Preventive Medicine Department, Federal University of Sao Paulo, ⁴Preventive Medicine Department, Medicine School of Ribeirao Preto, ⁵Preventiv
Background: Microalbuminuria may reflect diffuse endothelial damage. Considering that diabetes and hypertension cause vasculopathy, we investigated associations of albumin-to-creatinine ratio (ACR) with plasma glucose and blood pressure levels in high-risk subjects for metabolic syndrome. Methods: A sample of 519 (246 men) Japanese-Brazilians (aged 60 ± 11 years), who participated in a population-based study, had their ACR determined in a morning urine specimen. Backward models of multiple linear regression were created for each gender including log-transformed values of ACR as dependent variable; an interaction term between diabetes and hypertension was included. Results: Macroalbuminuria was found in 18 subjects. ACR mean values for subjects with normal glucose tolerance, impaired fasting glycemia, impaired glucose tolerance and diabetes were 9.9 ± 6.0, 19.0 ± 35.4, 20.7 ± 35.4, and 33.9 ± 55.0 mg/g, respectively. Diabetic subjects showed higher ACR than the others (p < 0.05). An increase in the proportion of albuminuric subjects was observed as glucose metabolism deteriorated (4.9, 17.0, 23.0 and 36.0%). Stratifying into 4 groups according to postchallenge glycemia (< 7.8 mmol/l, n = 91; ³ 7.8 mmol/l, n = 410) and hypertension, hypertensive and glucose-intolerant subgroups showed higher ACR values. ACR was associated with gender, waist circumference, blood pressure, plasma glucose and triglyceride (p < 0.05); albuminuric subjects had significantly higher levels of such variables than the normoalbuminuric ones. In the final models of linear regression, systolic blood pressure and 2-hour glycemia were shown to be independent predictors of ACR for both genders (p < 0.05). In men, also waist was independently associated with ACR. No interaction was detected between “diabetes and hypertension”. Conclusions: These findings suggest that both glucose intolerance and hypertension could have independent but not synergistic effects on endothelial function – reflected by albumin loss in urine. Such hypothesis needs to be confirmed in prospective studies.

Abstract

R. Agarwal

Division of Nephrology, Department of Medicine, Indiana University and RLR VA Medical Center, Indianapolis, IN, USA
Background: Oxidative stress is implicated in the pathogenesis of chronic kidney disease (CKD) and essential hypertension (EHTN). However, the role of hypertension in causing increased oxidative stress in patients with CKD is unknown. Methods: We performed a case control study in patients with EHTN and those with equal blood pressure assessed by ambulatory blood pressure monitoring but with concomitant CKD. Those with diabetes mellitus and those taking renin angiotensin inhibitors were excluded. Biomarkers of oxidative stress, malondialdehyde (MDA) and protein carbonylation and total glutathione levels were measured. Results: Average (SD) 24-hour ambulatory blood pressure in 12 patients with CKD was 134 (17)/75 (16) compared to 134 (10)/80 (9) in 11 patients with EHTN (p = NS). Plasma MDA in CKD was 0.89 ± 0.38 mmol/l compared to 0.68 ± 0.16 mmol/l in EHTN (p = 0.07). Urinary MDA/creatinine ratio was 1.78 (0.31) in CKD vs 1.43 (0.69) mmol/g in those with EHTN (p = 0.04). Thus, lipid peroxidation was increased in urine of CKD patients. Patients with CKD had higher (1.04 (0.20) nmol) carbonyl/mg protein compared to those with EHTN (0.80 (0.21) nmol carbonyl/mg protein) (p = 0.03). Thus, protein carbonylation was increased in CKD patients. Total glutathione in CKD and EHTN patients was 6.6 (1.8) ng/ml and 7.3 (3.1) ng/ml (p = NS). There was a good correlation between biomarkers of lipid (MDA) and protein oxidation (protein carbonyls) (r = 0.6, p = 0.004). Conclusions: Biomarkers of lipid and protein oxidation are higher in patients with CKD compared to EHTN despite similar blood pressure. Thus, nonhemodynamic factors such as inflammation and altered cellular redox state may play a greater role in the generation of oxidative stress in CKD.

Abstract

L. Djukanovic, D. Bukvic and I. Maric

¹Clinic of Nephrology, Clinical Center of Serbia, Beograd, and
²Institute of Endemic Nephropathy, Lazarevac, Serbia and Montenegro
Background/aims: Symmetrically shrunken kidneys have been considered as one of the characteristics of Balkan endemic nephropathy (BEN), but there is no agreement when the shrinking does occur in the course of the disease. In the present study, the relation between creatinine clearance (Ccr) and kidney length was compared between the patients in the early phase of BEN and other renal diseases. Methods: The study included 84 patients with BEN (39 males, aged 54 ± 12 years), 31 patients with other renal diseases (15 males, aged 54 ± 14 years) and 15 healthy subjects as controls. Only the patients with Ccr above 90 ml/min were included into the study. The kidney length was measured by sonography using sector sound of 3.5 MHz. Results: In healthy controls and patients with renal disease other than BEN, Ccr varied between 90 and 177 ml/min, and only 3 patients had Ccr above 150 ml/min. On the contrary, 15 (18%) BEN patients had Ccr between 90 and 120 ml/min, and 37 (44%) BEN patients had Ccr above 150 ml/min. Sonographically measured kidney length of all healthy subjects and patients with renal diseases other than BEN was above 10.5 cm. Out of 84 BEN patients, 21 (25%) patients had kidney length less than 10.5 cm. Conclusion: BEN patients in the early phase of the disease had significantly higher Ccr and smaller kidney in comparison to the patients with other renal diseases.

Abstract

D. Batinic¹, D. Milosevic¹, P. Konjevoda², L. Nizic¹, K. Vrljièak¹, M. Matkovic¹, D. Batinic¹ and L. Grkovic¹

¹University Children’s Hospital, Nephrology Department, and
²Institute Ruder Boskovic, Zagreb, Croatia
The urine saturation is considered as the better parameter for the estimation of risk of urolithiasis than any single urinary constituent. However, the determination of urine saturation is unsuitable for routine clinical practice. To evaluate a simpler and cheaper test than urine saturation for distinguishing stone formers from healthy individuals, urinary citrate/calcium ratio was determined in 30 children with urolithiasis, 36 children with isolated hematuria, and 15 healthy control children. The ratio was significantly lower in urolithiasis group comparing to controls, and significantly higher in hematuria than in urolithiasis group. The cut-off points between normal children and children with urolithiasis, accuracy, specificity and sensitivity were determined and compared with those of the urine saturation calculated with the computer program EQUIL 2. The data mining Weka software was used for the determination of the cut-off points. Children with urolithiasis had citrate/calcium ratio below 1.38 and urine saturation above 5.285. The citrate/calcium ratio showed in comparison to urine saturation similar high accuracy (91.11 vs. 88.89%), somewhat lesser specificity (73.33% vs. 93.33%) and much better sensitivity (100% vs. 86.89%) in discrimination of stone formers from normal children. The advantage in comparison to urine saturation is that it can be easily performed in clinical practice.

Abstract

R. Provenzano¹, L. Garcia-Mayol², P. Suchinda³, B. Von Hartitzsch⁴, S.B. Woollen⁵, R. Zabaneh⁶, J.C. Fink⁷ and the POWER Study Group

¹Department of Nephrology, St. John Hospital and Medical Center, Detroit, Michigan, ²Internal Medicine and Nephrology, Coral Gables, Florida, ³Carolina Diabetes and Kidney Center, Sumter, South Carolina, ⁴Tulsa Nephrology, Inc., Tulsa, Oklahoma, ⁵Nephrolo
Background and aim: Anemia occurs in approximately 47% of patients with chronic kidney disease (CKD) not on dialysis. Recombinant human erythropoietin (r-HuEPO, epoetin alfa) has been proven safe and effective for anemia treatment in patients with CKD using a three times-weekly regimen. The current study was conducted to evaluate the clinical safety and efficacy of a less frequent dosing regimen (once weekly) in this population. Methods: This prospective, multicenter, open-label, non-randomized study enrolled 1,557 adult anemic (hemoglobin (Hb) £10 g/dl) CKD patients not on dialysis. Epoetin alfa 10,000 U was administered subcutaneously once weekly for 16 weeks. Titration to 20,000 U once weekly at week 5 was permitted if patients had an increase in Hb < 1 g/dl. Safety and efficacy were assessed by changes in health-related quality of life (Linear Analog Scale Assessment (LASA) and Kidney Disease Questionnaire (KDQ)), changes in hematologic parameters and transfusion utilization, and incidence and severity of adverse events. Results: 1,338 patients were evaluable for efficacy. Mean Hb level increased from 9.1 g/dl at baseline to 11.6 g/dl at study completion (last observed value after baseline) (p < 0.0001). Overall, 89.8% of patients responded to once-weekly dosing, exhibiting an increase in Hb level of ³ 1 g/dl from baseline. The percentage of patients that required transfusion decreased from 11.1% (baseline) to 3.7% (during the study) (p < 0.0001). All quality-of-life parameters improved significantly from baseline (p < 0.0001). Mean LASA scores for energy, activity and overall quality of life increased from baseline to study completion by 27.9 mm (70.5%), 24.5 mm (57.0%) and 22.6 mm (47.4%), respectively. All 5 KDQ domains showed statistically significant improvements (p < 0.0001). Hb change was a strong predictor for all 5 KDQ domains and the overall score (p < 0.0001). Treatment with once-weekly epoetin alfa was well tolerated, similar to that reported with three times-weekly dosing. Conclusion: Once-weekly epoetin alfa therapy is safe and effective for treating anemia in patients with CKD not on dialysis, and is associated with significant improvements in functional status and quality of life.

Abstract

P.M. Hannula¹, I.H. Pörsti¹,², H.H.T. Saha¹, J. Kalliovalkama³,⁴, P.M. Jolma³, P. Kööbi³, R.-M. Ölander⁵ and J.A. Antonen¹

¹Department of Medicine, Medical School, University of Tampere, and/or Department of Internal Medicine, Tampere University Hospital, Tampere, ²Department of Internal Medicine, Division of Nephrology, Helsinki University Central Hospital, Helsinki, ³Depart
Aims: Immune dysfunction is characteristic of renal failure, leading to suboptimal antibody generation and increased susceptibility to infections. We tested whether the treatment of uremic phosphate retention by increased calcium carbonate intake will beneficially influence vaccination response in 5/6-nephrectomized rats. Methods: The nephrectomized (uremic) and sham-operated (control) rats were either fed 0.3% calcium diet (NTX and Sham groups, respectively) or 3% high-calcium diet (Ca-NTX and Ca-Sham groups). All rats were immunized with tetanus toxoid 6 weeks after the operations, and antitoxin levels were measured 7 weeks later. Results: Plasma creatinine was significantly elevated after the nephrectomy: the values (mean ± SD) in the NTX (n = 16), Ca-NTX (n = 11), Sham (n = 14) and Ca-Sham (n = 8) groups were 97 ± 14, 93 ± 17, 66 ± 7, and 69 ± 8 mmol/l, respectively. The NTX group developed phosphate retention and secondary hyperparathyroidism, which were completely prevented by the high calcium diet. The mean tetanus antitoxin concentrations of the groups were: NTX 0.25 ± 0.32; Ca-NTX 0.45 ± 0.44; Sham 0.58 ± 0.24 and Ca-Sham 0.64 ± 0.25 IU/ml (log of geometric mean concentration). The antibody response in the NTX group was significantly lower, i.e. 43% of that in the Sham group (p = 0.003), while the response in the Ca-NTX group was not different from that in the Sham group. The tetanus response of all the uremic rats inversely correlated with the plasma levels of phosphate (r = –0.447, p = 0.02), parathormone (r = –0.409, p = 0.03) and creatinine (r = –0.578, p = 0.002). Discussion: We conclude that renal failure impairs vaccination response in rats, the impairment of which can be favorably modulated by phosphate-binding and PTH-suppressing high-calcium diet.

Abstract

M.S. Sever, E. Erek, R. Vanholder, M. Koc, M. Yavuz, N. Aysuna, H. Ergin, R. Ataman, M. Yenicesu, B. Canbakan, C. Demircan and N. Lameire

¹Local Coordinator for the Renal Disaster Relief Task Force (RDRTF) for the International Society of Nephrology (ISN), Department of Nephrology, Istanbul School of Medicine, Istanbul, Turkey, ²Department of Nephrology, Turkish Society of Nephrology, Cerra
Background: During catastrophic earthquakes, crush syndrome is the second most frequent cause of death after the direct impact of trauma. The Marmara earthquake, which struck Northwestern Turkey in August 1999, was characterized by 639 crush syndrome victims with acute renal problems. The factors influencing their final outcome have been the subject of this study. Patients/methods: Within the first week of the disaster questionnaires asking about 63 clinical and laboratory variables were sent to 35 reference hospitals that treated the victims. Information obtained by means of these questionnaires, including the factors with a potential influence on outcome, was submitted to analysis. Results: Overall mortality rate was 15.2%. In univariate analysis, nonsurvivors were older (p = 0.048); the highest mortality rates were observed among the victims coming from the closest cities to the reference hospitals. Admission within the first 3 days of the disaster (p = 0.016), with oliguria (p = 0.042), lower figures for blood pressure (p < 0.001), platelets (p = 0.004) and serum albumin (p = 0.005) were associated with mortality. Also, higher body temperature (p = 0.013) and serum potassium (p < 0.001) as well as suffering from thoracic or abdominal traumas, extremity amputations and medical complications other than renal failure (for all 4: p < 0.0001) in addition to need of dialysis support (p = 0.015) and mechanical ventilation (p < 0.0001) indicated higher risk of death. In the multivariate analysis, age (p = 0.030, OR = 1.02), presence of disseminated intravascular coagulation (p = 0.001, OR = 4.49), abdominal trauma (p = 0.012, OR = 4.05) and amputations (p = 0.010, OR = 2.81) were predictors of mortality. Dialyzed patients were characterized by higher mortality rates than nondialyzed victims (17.2% versus 9.3%, p = 0.015). Conclusion: Outcome of the renal victims of catastrophic earthquakes is influenced by the type of trauma, comorbid events and complications observed during the clinical course as well as epidemiological features such as age, distance to reference hospitals and time lapse between disaster and admission to reference hospitals.

Abstract

M. Karim, P. Hill, G. Pillai, K. Gatter, D.R. Davies and C.G. Winearls

¹Oxford Kidney Unit, The Oxford Radcliffe Hospitals NHS Trust, ²Nuffield Department of Clinical Laboratory Sciences, University of Oxford, and ³Department of Cellular Pathology, The Oxford Radcliffe Hospitals NHS Trust, Oxford, UK
We describe 2 patients with mantle cell lymphoma who presented with dialysis-dependent acute renal failure and in whom the renal biopsies showed proliferative glomerulonephritis. The first patient had lymphadenopathy and the second splenomegaly, but no cause was initially identified in either case. The first patient was treated with immunosuppressive drugs, the second was given no specific therapy; renal function recovered in both. However, more than 1 year later, both again became dialysis-dependent but had also developed generalized lymphadenopathy. A diagnosis of mantle cell non-Hodgkin’s lymphoma was made in both cases. The association of active lymphoma and renal disease supports a paraneoplastic mechanism for the occurrence of the glomerulonephritis in these patients. The literature describing the association between non-Hodgkin’s lymphoma and glomerulonephritis is reviewed.

Abstract

T. Nakamura, Y. Kawagoe, T. Matsuda, Y. Ueda and H. Koide

¹Department of Medicine, Shinmatsudo Central General Hospital, Chiba, ²Department of Pathology, Dokkyo Koshigaya Hospital, Dokkyo University School of Medicine, Saitama, and ³Department of Medicine, Koto Hospital, Tokyo, Japan
A 49-year-old women with arteriosclerosis obliterans (ASO) complicated with light chain deposition disease (LCDD) is described. Renal biopsy showed a diffuse mesangial nodular lesion and tubulointerstitial changes. Congo red and l light chain staining were negative; however, the k light chain was positive in both glomeruli and tubular basement membranes by immunostaining. Using electron microscopy, electron-dense materials were found within glomerular basement membrane, mesangium and tubular basement membrane. The patient had renal dysfunction and nephrotic syndrome with progressive skin ulcers in the left leg. The patient was diagnosed as ASO with LCDD. She received low-density lipoprotein (LDL) apheresis once weekly for 10 consecutive weeks. Serum total cholesterol and phospholipid levels were decreased, and serum creatinine and blood urea nitrogen levels also tended to decline after treatment. Urinary protein excretion was reduced markedly, and hypoalbuminemia was also improved. Ischemic symptoms including leg pain and leg coldness and numbness improved after apheresis. The walking distance increased on a treadmill. The skin temperature was increased from 33.8 °C to 35.5 °C after apheresis and the skin ulcers were also improved. Plasma nitric oxide (NO) levels were increased from 66.0 mM/l to 88.0 mM/l and plasma endothelin (ET)-1 levels were decreased from 14.5 pg/ml to 5.8 pg/ml after apheresis. LDL apheresis was effective in ameliorating hyperlipidemia, massive proteinuria, hypoalbuminemia and high serum creatinine levels in an LCDD patient with nephrotic syndrome. Furthermore, we showed beneficial effects of LDL apheresis on skin ulcers due to ischemia in an ASO patient complicated with LCDD.

Abstract

F. Bridoux, X. Kyndt, R. Abou-Ayache, B. Mougenot, S. Baillet, M. Bauwens, V. Lemaitre, J.-M. Goujon, G. Touchard and P. Vanhille

¹Department of Nephrology, Hôpital Jean Bernard, Poitiers, ²Department of Nephrology, Centre Hospitalier Général, Valenciennes, ³Department of Pathology, Hôpital Tenon, Paris, and ⁴Department of Pathology, Hôpital Jean Bernard, Poitiers, France
Tubulointerstitial nephritis is the most common renal complication in primary Sjögren’s syndrome (SS). It is usually associated with symptoms of distal tubular dysfunction, type I (distal) renal tubular acidosis (RTA) and nephrogenic diabetes insipidus. Proximal tubular abnormalities are considered to be less frequent, and Fanconi’s syndrome has been only exceptionally reported in patients with SS. We describe 2 patients with primary SS, characterized by xerostomia, dry eyes, extensive lymphocytic infiltrate on salivary gland biopsy, positive tests for anti-SSA/SSB antibodies and/or antinuclear antibodies, who presented in renal failure with proteinuria, microscopic hematuria and type I RTA. Further studies revealed proximal tubular dysfunction, including renal glucosuria, generalized aminoaciduria, phosphaturia, uricosuria, together with proximal (type II) RTA in 1 case. Neither of these patients had Bence Jones proteinuria or monoclonal gammopathy. Kidney biopsy showed focal proximal tubulitis, associated with proximal tubular cell atrophy and dedifferentiation, and diffuse interstitial nephritis with fibrosis. No significant glomerular or peritubular deposits of immunoglobulin light or heavy chain were observed. These findings demonstrate that diffuse, distal and proximal, tubular dysfunction may occur in patients with SS and interstitial nephritis. Lymphocytic infiltration of proximal tubular cells is probably involved in the pathogenesis of Fanconi’s syndrome in SS. However, the mechanisms involved in the alteration of sodium-dependent apical transports remain to be elucidated.

Abstract

H. Ashrafian and R.G. Bogle

Department of Cardiology, Ealing Hospital, London, UK
Lithium is still the treatment of choice in bipolar affective disorder. The patient presented here represents an example of the possible severity of metabolic defects resulting from lithium use. In this case, it caused severe intractable nephrogenic diabetes insipidus (NDI). Our case report draws attention to 2 important messages. The first is the complexity in treating psychiatric patients that is often not borne out in the medical literature. The second is the role and power of pharmacological augmentation. While the role of these agents has been appreciated for some time, the use of carbamazepine and of drug combinations is not as well recognized. We emphasize the clinical features of NDI, lithium’s metabolic sequelae and furthermore collate the most up-to-date account of the signalling effects conferred by these agents in a summary diagram.

Abstract

T. Apostolou, F. Sotsiou, G. Dimitriades, N. Nikolopoulou, K. Chilal, M. Balanika, P. Yiannopoulos and V. Hadjiconstantinou

¹Nephrology, ²Pathology, ³Anesthesiology and ⁴²nd Surgery Department, “Evangelismos” General Hospital, Athens, Greece
A case of severe acute renal failure in a young female patient necessitating renal replacement therapy after laparoscopic cholecystectomy is described. The histology of the renal lesion assigned to the effects of laparoscopic surgery is relevant for the pathogenesis of renal complications after such procedures. This explains part of the pathogenesis of the ischemic lesions in kidney structure that increased intra-abdominal pressure can provoke. Emphasis is given on the prevention of such side effects.

Abstract

K.H. Katsanos, J. Theodorou, K.P. Katopodis and K.C. Siamopoulos

Abstract

M. Galler, M.H. Schwenk, K.C. Parthiban and W. Palecki

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Volume 61, No. 6/2004(June)