Yuichi Kitano

Population analysis of mesothelium in situ and in vivo exposed to bicarbonate-buffered peritoneal dialysis fluid.

Population analysis of mesothelium (PAM) done using the in vivo and almost in situ technique of mesothelial cell imprints revealed that lactate-buffered solutions had detrimental effects upon cell viability, that high glucose concentration affected cytokinesis, whereas the association of both components led to a decreased density population of cells showing a larger surface area. In the present study, PAM was done on mesothelium of mice exposed to bicarbonate-buffered peritoneal dialysis fluid (BBF) with glucose concentrations of 1.5 and 4.25%, for periods of time of 2 h, 15 and 30 days, as well as after recovery intervals of 7 and 30 days, BBF did not affect mesothelial cell viability. However, the increased incidence of multinucleated cells observed with both glucose concentrations, more marked with the 4.25% solution, suggests a detrimental effect upon the mechanism of cytokinesis. Furthermore, the higher the glucose concentration, the higher the mean-cell cytoplasmic surface area and the proportion of large cells, both resulting most probably from the regulatory volume increase developed by cells continuously exposed to hyperosmolar fluids. So far, evidence presented in this study suggests once more that BBF is remarkably more compatible with a higher quality of adaptation and survival of the exposed mesothelium than the lactated fluid. The question of whether the alterations induced by the high concentration of glucose result from a specific effect of glucose, by the coincidental hyperosmolarity, or by both still remains unanswered.

Malignant Hypertension and Antiphospholipid Syndrome

Dr. A.E. Sirvent, Avda Orihuela 4, 6 D, E-03006 Alicante (Spain) Dear Sir, The kidney is now recognized as another target organ in the antiphospholipid syndrome (AS) [1]. Renal involvement is consistent with thrombosis of the major renal vessels and noninflammatory microvascular disease [2-4]. In the clinical findings renal failure has been emphasized over systemic hypertension. We report here on a patient with systemic malignant hypertension and throm-botic microangiopathy (TM) with no other occlusive complications. A 29-year-old man was hospitalized with acute renal failure during a malignant hypertensive episode, after developing hypertension in the 3 months prior to admission. Thrombocytopenia was also detected. Physical examination showed: blood pressure 230/ 130 mm Hg, grade IV retinal changes, no abdominal bruits were heard; the signs were compatible with congestive heart failure. The most significant laboratory findings were: hemoglobin lOg/dl, WBC 14,000/μl (normal differential count), platelets 47,000/μl, normal coagulation tests, fíbrinogen 490 mg/dl and schistocytes on a peripheral blood smear. Urea was 35 mmol/l, creatinine 884 μmol/l, LDH 971 U/l, haptoglobin 11 mg/dl, and urine contained proteinuria 2.1 g/day, 10-15 erythrocytes/hpf. Chest X-ray revealed pulmonary edema and cardiomegaly, and echo-cardiography indicated left ventricular hypertrophy, normal ejection fraction and mild mitral regurgitation. The abdominal ultrasound showed a right kidney of 11.9 cm and a left kidney of 8.7 cm. No evidence of kidney infarction was seen in the renal CT scan. The magnetic resonance angiogram disclosed normal aorta and renal arteries. The following laboratory data were negative or normal: urine cultures, urine catecholamines and VMA, HBsAg, serology for HCV, cryoglobulins, rheumatoid factor, ANCA, anti-GBM, ANA, anti-DNA, anti-SSA (Ro), anti-SSB (La), anti-Sm, anti-RNP antibodies, C3, C4, VDRL, brain CT, cystography, lupus anticoagulant; anticardiolipin antibodies (aCL) IgG 63.3 GPL/ml (n.v. < 23), IgM 3.1 MPL/ml (n.v. < 11), and repeated after 8 weeks, IgG 40 GPL/ml (ELISA). Antiplatelet antibodies were positive. The kidney biopsy showed TM; no deposits were noted in the immunofluores-cence study. Blood pressure was controlled. An increase in platelets and normalization of LDH was achieved following plasma exchange with FFP as the replacement fluid; upon withdrawal of the plasma exchange, thrombocytopenia recurred. After receiving the aCL determination

Sensitivity to Calcium Intake in Calcium Stone Forming Patients

The absorptive or renal origin of hypercalciuria can be discriminated using an acute oral calcium load test (ACLT). Of 86 patients with calcium oxalate kidney stones, 28 (23%) were found to be hyperca

Effects of ACE inhibitor on renal anemia in predialysis patients.

Shinsuke Nomura, MD, Nephrology Division, Department of Medicine, Kawasaki Medical School, Kurashiki, Okayama 70101 (Japan) Dear Sir, The role of angiotensin-converting enzyme inhibitors (ACEI) in inducing anemia has been reported in people with normal renal function [1], in patients with chronic renal failure on hemodialysis [2] and in kidney transplant patients [3, 4]. Several mechanisms of ACEI-induced anemia have been hypothesized. ACEI may decrease angioten-sin II, which stimulates erythropoietin production. They may decrease renal tissue hyp-oxia due to their property for increasing renal blood flow. Or, by decreasing renin levels, they may diminish one likely precursor of erythropoietin [2, 5]. The association between renal anemia and ACEI in patients at the predialysis stage has not been well discussed. Therefore, we carried out a retrospective analysis of 39 predialysis patients checking their medical records during the follow-up period at our outpatient clinic. Among patients in whom regular renal replacement therapy had been initiated from 1984 to 1993 at Kawasaki Medical School Hospital, 39 Japanese patients (23 males) were entered into the study with the following restrictive criteria: (1) age 30-65; (2) followed up by us from when serum creatinine level had been less than 2.0 mg/dl to the initiation of renal replacement therapy; (3) never showed microcytic hypochromic anemia during the period; (4) had no malignancies, liver cirrhosis, or collagen diseases, (5) no anabolic steroid, recombinant human erythropoietin (rhEpo) or transfusion was given during the period. Patients with diabetic ne-phropathy and polycystic kidney disease were excluded from the study. Twenty of them had chronic glomerulonephritis or nephrosclerosis diagnosed by renal biopsy. When their serum creatinine level increased to over 3.0 mg/dl (phase A) and over 7.0 mg/dl (phase B), the patients were divided into three groups according to the medication they were taking for hypertension: group 1 (no antihypertensive agents was prescribed): group 2 (ACEI was prescribed for at least over 2 months), and group 3 (other antihypertensive agent(s) was prescribed, such as calcium antagonists, α-and ß-blockers). Most of the prescribed ACEI were capto-pril or enalapril. Patients in whom ACEI was prescribed in combination with other agents were put into group 2. As shown in figure 1 ‚ the hematocrit level of group 2 at phase B was significantly lower than in group 1, while no difference was found at phase A (unpaired t test). There was no difference in

Long-term erythropoietin in rats with reduced renal mass

Hematocrit increase with recombinant erythropoietin (rEPO) has been associated with increased progression of renal insufficiency in experimental models of renal mass reduction. The aim of the present study was to assess the effects of therapy with rEPO and various antihypertensives on the progression of chronic renal insufficiency and on arterial hypertension in an experimental model of renal mass reduction. Rats subjected to a two-thirds nephrectomy were randomly assigned to an untreated control group or to therapy with rEPO (subcutaneously, at an initial dose of 40 U/kg thrice weekly), rEPO plus verapamil (subcutaneously, 0.5 mg/kg/day), or rEPO plus enalapril (orally, 50 mg/l in the drinking water). Combining enalapril and rEPO therapy controlled systemic blood pressure (BP) and the increase in proteinuria. Glomerular injury, as assessed 16 weeks after renal ablation, was more marked in the animals treated with rEPO with or without either antihypertensive. The morphometric analyses showed greater glomerular tuft areas in the three groups receiving rEPO than in the controls. The glomerular tuft area was directly correlated with the rate of glomerulosclerosis. In about 11% of the rEPO-treated hypertensive rats, the lesions showed severe hypertensive vasculopathy; in the animals treated with rEPO plus enalapril, the lesions were less severe. We conclude that therapy with rEPO was associated to renal damage which could not be attenuated by enalapril despite controlling BP and proteinuria, and may have a nonhemodynamic cause. Therapy with rEPO might trigger lesions usually associated with severe arterial hypertension; concomitant therapy with enalapril attenuates hypertensive vasculopathy.

Severe Hypothyroidism Masquerading as Renal Impairment

A case of severe hypothyroidism in a 51-year old male is presented. The patient was especially complaining of weakness, stiffness and moderate pain in the proximal muscle groups together with rhinorrhea and nasal stenosis. Because of severely elevated S-creatine-kinase combined with reduced creatinine clearance and proteinuria, polymyositis with secondary glomerulopathy was suspected. Meanwhile, biopsies from skin, muscle, and kidney were normal. All symptoms disappeared 3 months after thyroid replacement therapy was initiated. S-TSH should be considered when evaluating patients with renal impairment of unknown etiology.

Acute glomerulonephritis without fever: an unusual presentation of malaria on mefloquine prophylaxis.

Dr. J.C. Martínez-Ocaña, Department of Nephrology, Hospital Universitari Germans Trias i Pujol, Ctra. del Canyet, s/n, E-08916 Badalona, Barcelona (Spain) Dear Sir, The delayed presentation of malaria due to Plasmodiumfalciparum has recently been suggested in travellers on prophylaxis with mefloquine [1]. We report on a traveller, returning from Togo, using this drug who presented with acute glomerulonephritis as the initial and delayed manifestation of malaria due to Plasmodium malariae. A previously healthy 24-year-old white male, who was born and raised in Barcelona (Spain), was admitted on October 6, 1994, with a 2-day history of palpebral and ankle edema with generalized myalgia after returning from 1-month trip to Togo 35 days before. He had received prophylaxis with mefloquine for 1 week before the trip and 4 weeks afterwards. No fever was noted. On admission, blood pressure was 170/120 mm Hg, but the physical examination was unremarkable. Laboratory tests showed: ESR, 9mm/h; hemoglobin, 127 g/l (12.7 g/dl); white blood count, 6.9 × 109/l(6,900/mm3); platelet count, 147 × 109/1 (147,000/mm3); blood urea, 14 mmol/l (84 mg/dl); serum cre-atinine, 140μmol/l (1.6 mg/dl); total proteins, 58 g/l (5.8 g/dl); albumin, 33 g/l (3.3 g/ dl); CK, 126 U/l; AST, 53 U/l; ALT, 126 U/l; alkaline phosphatase, 91 U/l; GGT, 28 U/l, and total bilirubin, 11 μmol/l (0.6 mg/dl). Urinalysis revealed 15-20 red blood cells (RBC)⁄field. Proteinuria was 0.5g/24h. Chest film was normal. Normal kidneys were evident on abdominal ultrasonography. Serologies for hepatitis A, B, and C, HIV, syphilis, citomegalovirus, Toxoplasma, Bru-cella and Salmonella were negative. Immunology revealed: C3, 19 g/dl (normal range 52-120); C4, 8.7 mg/dl (18-49); CH50, < lOU/ml (80-140); positive C3 nephritic factor; IgG, 1,285 mg/dl (700-1,500); IgA, 265 mg/dl (88410); IgM, 129 mg/dl (50-240); circulating immunocomplexes, 2.3 ng/ ml (normal range < l .5), and negative antinu-clear antibodies, ANCA, rheumatoid factor and antistreptolysins. Frusemide and nifedi-pine were given and renal function improved. He remained asymptomatic until November 29, 54 days after the initial presentation, when malaise, fever and macroscopic hematuria appeared. The patient was readmitted. Physical examination was normal except for intermittent fever of up to 40 °C and chills every 48 h. Analysis showed: blood urea, 6.8 mmol/l (41 mg/dl); serum creatinine, 138μmol/l (1.6 mg/dl); proteinuria,

Leg Ulceration during Amezinium Methyl Sulfate Therapy for Hypotension in a Hemodialyzed Patient with Generalized Vascular Calcification

Shinsuke Nomura, MD, Nephrology Division, Kawasaki Medical School, Kurashiki, Okayama 701-01 (Japan) Dear Sir, Hypotension is a common problem in patients with end-stage renal disease undergoing hemodialysis. In addition to hypo-volemia and acetate toxicity, abnormalities in the systemic nervous system may contribute to the pathogenesis of hemodialysis-induced hypotension. Amezinium methyl sulfate, an indirectly acting sympathomi-metic drug [1], is often used to treat the hypotension of hemodialyzed patients [2]. It can stimulate the α-receptors of vessels and cardiac ß-receptors and elevates the blood pressure. Therefore, patients treated with amezinium methyl sulfate may complain of palpitation and headache. We describe a hemodialyzed man in whom amezinium methyl sulfate seemed to contribute to chronic leg ulceration. Since this association has, to our knowledge, not been reported before, we would like to introduce this case. A 52-year-old man was admitted to our hospital having chronic painful leg ulcers which developed 7 months ago. He had been receiving hemodialysis for 22 years. His renal disease was thought to be chronic glo-merulonephritis, and he was not diabetic. He had several complications, such as secondary hyperparathyroidism, severe atherosclerosis, constrictive pericarditis, congestive heart failure, carpal tunnel syndrome, and chronic hepatitis, most of which were likely due to the long-term hemodialysis treatment. A serial X-ray film revealed generalized vascular calcification. He denied experiencing claudication, but the pulses of both the bilateral posterior tibial artery and the dorsalis pedis artery could not be detected on palpation. More than 20 months prior to this admission he had experienced hypotension, especially during the hemodialysis sessions, and amezinium methyl sulfate treatment (Ri-sumic, Dainippon Pharmaceutical Co., Ltd.) (20 mg/day) was initiated. After admission, local ulcer treatment was performed and prostaglandin administered for several weeks, but this was unsuccessful. However, after administration of amezinium methyl sulfate was stopped, the ulcers gradually decreased in size and number and healed completely during the next few weeks. Thermo-graphic studies revealed improvement of the local temperature of the lower extremities.

Kinetic study of glomerular cells of diabetic rats in relation to the development of irreversible glomerular sclerosis

In order to clarify the cellular kinetics involved in progression of diabetic glomerulosclerosis, the epithelial cells of spontaneously diabetic WBN/Kob rats were investigated by labeling with the DNA precursor bromodeoxyuridine, which was histochemically stained using monoclonal antibody. The labeling index (number of labeled cells/number of cells counted) of glomeruli was constantly low (approximately 0.15%) and no significant variation could be demonstrated in control rats of the Wistar strain. In both control and diabetic rats, podocytes showed no evidence of mitosis. In contrast to capillary podocytes, the Bowman epithelial cells of diabetic rats showed increased labeling, often surrounding sclerotic capillaries. These observations suggest a critical role of Bowmans epithelial cells in the development of irreversibly sclerotic glomeruli in diabetic nephropathy.

Effects of Dietary Salt Restriction on Blood Pressure and the Renal Vasoactive System in the Congenitally Bilateral Hydronephrotic Rat

We examined the responses on blood pressure when the renal vasoactive system such as renin-angiotensin-aldosterone system (RAAS) and kallikrein-kinin system (KKS) was activated by dietary salt restriction in the congenitally bilateral hydronephrotic rat (BHN). In a low salt diet (LS)-normotensive and normal kidney control rats after 8 weeks from initiating dietary salt restriction, the plasma sodium concentration (PNa) was retained at a level similar to that in the normal diet (ND)-control rats, and plasma renin activity (PRA), plasma aldosterone concentration (PAC) and urinary kallikrein activity (UKA) were about 1.8-, 9.4-and 1.7-fold higher, respectively, than those in the ND-control rats. In addition, LS-control rats had a significantly (p < 0.001) high systolic blood pressure (163 +/- 2.0 mm Hg) compared with that (136 +/- 5.8) of ND-control rats. These results suggest that the activated renal vasoactive system acted for not only sodium retention but also for elevation of blood pressure in LS-control rats. In LS-BHN at week 8, PNa was also retained at a nearly normal level. However, the renal vasoactive system activation for sodium retention was higher than that of LS-control rats; that is, increase of PRA, PAC and UKA were about 3.8-, 24.7-and 10.0-fold, respectively, than in ND-BHN. The higher activation of RAAS, nevertheless, does not affect blood pressure in BHN; that is, both hypertension of BHN fed LS and ND developed similarly. These findings suggest that dietary salt restriction could markedly activate the renal vasoactive system for sodium retention without elevating blood pressure in BHN different from control rats.