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PubMed1999

Expression of 90-kDa heat shock protein within regenerative tubular cells in a patient with acute oliguric renal failure due to malignant hypertension.

A 29-year-old man developed acute oliguric renal failure with severe hypertension and microangiopathy. He was treated with hemodialysis and anti-hypertensive drugs, but oliguria was prolonged. A renal biopsy was performed on the 29th hospital day. Small arteries and arterioles were characterized by marked intimal thickening, and most of the glomeruli showed ischemic changes. Although there was extensive tubular loss and atrophy, regenerative changes were occasionally observed in some tubules, in which 90-kDa heat-shock protein was induced. He was diagnosed as having malignant nephrosclerosis, and was treated with a prostaglandin I2 analog, in addition to anti-hypertensive drugs. Thereafter, his renal function recovered gradually, and hemodialysis was discontinued on the 49th hospital day. Functional recovery lasts more than five years. We suggest that the expression of HSP90 in regenerative tubular cells is a useful histological indicator for predicting recovery from acute oliguric renal failure due to malignant hypertension.

Acute Kidney Injury↗

PubMed1999

Analysis of factors influencing chronic renal failure progression.

One of the most important characteristics of chronic renal failure (CRF) is its progression to end stage renal disease. CRF progression depends of many factors indicated in numerous experimental and clinical studies. The present study was undertaken with the aim to examine the role of sex, etiology of CRF, renal function at the beginning of the study, hypertension and protein intake on CRF progression. Ninety-two patients (47 female and 45 male) aged between 17 and 70, with various underlying kidney diseases and various degrees of CRF were followed for 8 years. CRF progression was expressed as Creatinine clearance (CCr) and reciprocal values of serum Creatinine (SCr) against time. CRF progression was slower in women than in men, but not significantly. Patients with diabetic nephropathy (b = 0.00006) and glomerulonephritis (b = 0.00005) had faster progression of CRF than patients with nephrosclerosis (b = 0.00002), tubulointerstitial nephritis (b = 0.00003) and polycystic kidney disease (b = 0.00003). The fastest progression of CRF was in patients with the lowest SCr values at the beginning of the study. Proper regulation of blood pressure was the most important factor in slowing down CRF progression, independently of kind of antihypertensive drugs. Neither angiotensin converting enzyme inhibitors (b = -0.00001) nor calcium channel blockers (b = -0.00002) showed better effects on CRF progression slowing down in comparison with other antihypertensive drugs (b = -0.00001). Low protein diet slowed down CRF progression, but not significantly. In conclusion, our retrospective study confirms that CRF progression depends on sex, underlying renal diseases and serum Creatinine levels at the beginning of the study. Good regulation of blood pressure and low protein diet can slow down CRF progression.

Adolescent↗

PubMed1983

Renal aspects of treatment by converting enzyme inhibitors in hypertension.

Converting enzyme inhibitors (CEI) are efficient antihypertensive medications. The acute and chronic effects of captopril (SQ) on renal function and electrolyte balance are analyzed in the present paper. Acute administration of SQ was associated with renal vasodilatation in the patients with essential hypertension (EH) but had no effect in normal subjects with similar renin levels thus suggesting an enhanced renal vascular response to CEI in EH. A variable effect of CEI on renal function was observed in renovascular hypertension; GFR fell when blood pressure decreased by more than 25 mmHg. Three cases of striking recovery of GFR during chronic SQ in young patients with malignant nephrosclerosis maintained on hemodialysis are reported. Such an improvement in GFR never occurred in patients with primary renal disease. When systemic and renal responses to acute isotonic saline loading were assessed, captopril blunted the exaggerated natriuretic response to saline loading observed in EH and unmasked the volume-dependence of arterial pressure. A case of hyperkalemia during treatment with SQ is reported in a patient with bilateral renal artery stenosis who developed moderate renal failure during treatment. This was associated with high plasma aldosterone whilst fractional excretion of K+ was inappropriately low for the level of serum creatinine thus suggesting that tubular unresponsiveness to aldosterone may have developed during SQ.

Acute Disease↗

PubMed1993

Microalbuminuria in essential hypertension.

The prevalence and significance of microalbuminuria is not well elucidated in patients with essential hypertension. In newly detected hypertension, its prevalence ranges between 23 and 37% and albuminuria is usually well correlated with the level of arterial pressure. Interestingly, albuminuria is enhanced in overweight hypertensive patients. Antihypertensive treatment has variable influence on albuminuria, and converting enzyme inhibitors, in contrast to other agents, tend to partially correct this abnormality. Whether microalbuminuria represents a predictor of the future development of nephrosclerosis and ultimately renal failure, or a predictor of cardiovascular morbidity deserves to be investigated.

Albuminuria↗

PubMedDate not supplied

Renal surrogates in essential hypertension.

The kidney can be considered both as culprit and victim in the hypertensive process. Renal functional derangement contributes to the development of arterial hypertension and the development of secondary vascular damage both at the glomerular and arteriolar level accounts for the development of progressive nephrosclerosis. The most common alteration of renal function observed in humans since the early stages of essential hypertension is the presence of renal vasoconstriction. This can be accompanied by the appearance of hyperuricemia, increased urinary excretion of enzymes such as N-acetyl-beta- glucosaminidase and of proteins like albumin and beta2-microglobulin. Later on, a progressive fall in glomerular filtration rate accompanied or not by proteinuria can be observed if high blood pressure persists.

Albuminuria↗

PubMed2000

Combination of non-hypotensive doses of valsartan and enalapril improves survival of spontaneously hypertensive rats with endothelial dysfunction.

There is increasing evidence to suggest endothelial dysfunction as a critical factor in vascular diseases. Genetically predisposed spontaneously hypertensive rats (SHR) treated with inhibitors of nitric oxide (NO) synthase, develop a severe hypertensive nephrosclerosis without the necessity for surgical reduction in renal mass, nephrectomy, renal infarction or nephrotoxic drugs. In these animals, endothelial dysfunction is considered a valid model for assessment of the efficacy of cardiovascular therapy. SHR were treated with either the angiotensin-converting enzyme inhibitor enalapril or the angiotensin II (Ang II) AT(1)-receptor antagonist (AIIA) valsartan at sub-hypotensive doses and the effects on survival rates, cardiac and renal changes were monitored. Rats treated with valsartan, alone or in combination with enalapril, showed markedly higher survival rates (67-85%, respectively) than untreated animals (37%) or those treated with enalapril alone (55%). Valsartan at a dose which attenuated blood pressure increase led to even greater survival rates (95%). Despite these improved survival rates, at non-hypotensive doses the drugs had no effect on histological appearance, nor was kidney function improved. Plasma creatinine levels were reduced by valsartan, alone or in combination with enalapril, but proteinuria persisted with all treatments over the 12 weeks of the study. Aldosterone levels were significantly reduced by all treatments. The results suggest a beneficial role for endothelium in hypertension. Reduced renal perfusion pressure probably underlies the beneficial renal effects of high-dose valsartan.

Aldosterone↗

PubMed1988

Multicenter report on dialysis and transplantation in Korea, 1986. Korean Society of Nephrology.

Since 1981, the Korean Society of Nephrology began annual report on renal replacement therapy in Korea. The annual number of new patients receiving dialysis treatment in 1986 increased to 957 patients (23.3 per million population) from 825 patients (20.4 per million population) in 1985. And the total number of patients on replacement therapy increased from 1,508 patients (37.3 per million population) to 2,534 patients (61.7 per million population). 1,340 patients (32.6 per million population) of these patients were on hemodialysis, 573 patients (13.9 per million population) on continuous ambulatory peritoneal dialysis (CAPD) and 621 patients (15.1 per million population) on functioning renal graft as of December 31, 1986. The common causes of renal failure of new patients were chronic glomerulonephritis (41.6%) followed by diabetic nephropathy (12.6%), nypertensive nephrosclerosis (7.8%), chronic pyelonephritis (2.5%) and others. The annual mortality rate decreased from 21.9% in 1981 to 13.5 in 1986. The common causes of death in patients on dialysis therapy were cardiac (32.8%), vascular (14.7%), infective (14.7%) and social problems (11.2%) in the order of frequency. Recently, the number of patients requiring dialysis is rapidly increasing due to expanded medical insurance support for dialysis and improved economic status of our country. Therefore, it is necessary to draw up counterplan for a rapid growth of the number of new patients.

Hepatitis B↗

PubMed2003

Angiotensin-converting enzyme inhibitor withdrawal and ACE gene polymorphism.

AIMS: Withdrawal of angiotensin-converting enzyme (ACE) inhibitors may affect the progression of chronic renal failure and an insertion/deletion (I/D) polymorphism of the ACE gene may influence it. METHODS: We retrospectively collected patients with chronic glomerulonephritis and benign nephrosclerosis who discontinued ACE inhibitor use. The relationship between the decline of renal function after the withdrawal and the influencing factors such as ACE gene polymorphism, blood pressure and proteinuria were evaluated using multiple regression analysis. RESULTS: Forty-two patients (initial serum creatinine 0.5 - 6.5 mg/dl) had been treated and discontinued ACE inhibitor use. Only patients with the II or DI genotypes of the ACE gene developed the deterioration of renal function, starting at 2 months after the withdrawal. Stepwise regression analysis revealed that the level of proteinuria after the withdrawal, presence of the insertion of ACE gene and serum creatinine level at the time of withdrawal mainly influenced the decline of renal function after the withdrawal (adjusted R2 = 0.48). CONCLUSION: Withdrawal of ACE inhibitor causes the deterioration of renal function in patients with the II or DI genotypes, high proteinuria after the withdrawal, and high serum creatinine level at the withdrawal, which probably causes the rebound increase in serum ACE activity.

Aged↗

PubMed1975

Chronic interstitial nephritis: etiologic factors.

Whether chronic interstitial nephritis (pyelonephritis) mainly results from kidney infection is widely debated. We studies 101 patients with interstitial nephritis, selected from 320 patients with newly diagnosed chronic renal disease, for frequency of etiological factors. Eleven had no etiologic factor(s) identified; 89 had clearcut factor(s): anatomic abnormalities 31, analgesic abuse 20, hyperuricemia 11, nephrosclerosis 10, stones 9, sickle cell disease1, tuberculosis 1, multiple causes7. Bacterial infection (present in 27%) was found only with another preceding primary cause of renal damage. Analgesic abusers frequently denied drug ingestion; 15% had urinary tract infection and 20% classical papillary necrosis. Two had family histories of analgesic abuse with nephropathy. We conclude that interstitial nephritis is a common form of chronic renal disease, is seldom idiopathic, rarely results from bacterial infection alone in adults, and frequently results from analgesic abuse in the United States.

Adolescent↗

PubMed1999

[A case report of diabetic scleredema in a patient with non-insulin-dependent diabetes mellitus].

A 70-year-old Japanese man with non-insulin-dependent diabetes mellitus showed scleredema diabeticorum. The patient complained of edematous feelings on his hands, both arms and face. The time of onset of these symptoms was not known. He had typical clinical and histopathological findings of diabetic scleredema. His diabetic control was poor and HbA1c level was 8.2% under insulin treatment. The patient had many complications such as diabetic retinopathy, diabetic nephropathy with benign nephrosclerosis, hyperlipidemia accompanied with a low level of high density lipoprotein cholesterol, hypertension and coronary heart disease. There were no abnormal laboratory findings except the diabetic controls and mild abnormal renal functions; however erythrocyte sedimentation rate was high.

Aged↗

PubMed1998

Clinicopathological study of renal involvement in patients with systemic sclerosis.

OBJECTIVE: To assess the incidence of renal involvement in patients with systemic sclerosis (SSc) as well as its clinical and pathological changes. METHODS: The renal involvement was studied clinicopathologically in 93 patients who were compatible with the diagnosis of SSc retrospectively. RESULTS: Eighteen patients (19.4%) were diagnosed as renal involvement by one or more of the following: proteinuria, renal hypertension, elevated levels of blood urea nitrogen (BUN) and/or serum creatinine (sCr). Renal impairment was observed in 5 patients (5.4%). The mortality rate was 12.9%, and 5 patients died of renal failure. Histological study was performed in 5 patients. The thickening of interlobular arterioles with intimal proliferation was found in 4 of the patients who also showed mild nonspecific glomerular changes. Two had no clinical features of renal involvement, 1 had renal hypertension and 1 died of renal failure. Another patient with a 22-year disease duration showed chronic glomerulonephritis with nephrosclerosis. CONCLUSIONS: SSc patients should be followed-up clinically and renal biopsy performed if necessary in order to discover early renal involvement and to insert rational therapy to improve its prognosis.

Adolescent↗

PubMed1999

Representation of blacks, women, and the very elderly (aged > or = 80) in 28 major randomized clinical trials.

OBJECTIVE: The purpose of this manuscript is to precisely quantify the representation of women, blacks, and very old (aged 80 or more) participants in 28 past or ongoing randomized clinical trials on hypertension, cardiovascular disease, renal disease, and diabetes mellitus. METHODS: Selection of the 28 studies was arbitrary, based primarily on the reference being often quoted or cited as relevant data for women, blacks, the elderly, or persons with diabetes mellitus. RESULTS: Twenty-three of the 28 studies enrolled a majority of men. Many of the completed trials had an under-representation of blacks (0% to 8%). An adequate number (1,091) of very old (aged 80 or more) persons have been studied for isolated systolic hypertension, but the number of such patients thus far studied for diastolic hypertension is too small to allow evidence-based recommendations for therapy. Reported studies in diabetes have included a majority of men (average, 58%) and four of the five trials reviewed enrolled relatively few blacks (average, 4.6%). CONCLUSIONS: Women, blacks, and the very old (aged 80 or more) have been under-represented in many past randomized clinical trials, but ongoing studies will resolve this discrepancy in most instances. The Women's Health Initiative (WHI) will provide data on 161,861 multi-ethnic postmenopausal women. ALLHAT results will include 15,133 hypertensive blacks, and AASK will have 1,094 hypertensive blacks with nephrosclerosis. ALLHAT, STOP-2, and HYVET will include more than 5,000 persons aged 80 or more. Future trials on diabetes mellitus must be designed to improve the representation of women and blacks.

Black or African American↗

PubMedDate not supplied

[Peritoneal dialysis in the aged].

INTRODUCTION: Patients older than 65 years represent the group of patients affected by end-stage renal failure characterized by the most rapid growth. The prevalent causes of end-stage renal disease (ESRD) in the elderly are diabetes mellitus and nephrosclerosis due to long-term arterial hypertension. There are a number of physiologic changes which occur with aging that might have an impact on the choice of renal replacement modality for an elderly patient: clinical or subclinical diminished cardiovascular reserve due to atherosclerosis or impaired baroreceptor function, slow deterioration of pulmonary function, impaired immunity, increased susceptibility to infection, metabolic disturbances, bone loss from osteoporosis, altered metabolism of protein and a variety of drugs, high rate of malnutrition, tendency to carbohydrate intolerance. MATERIAL AND METHODS: When choosing a dialysis regimen for an elderly patient, physiologic changes that occur with aging, specific medical conditions that are common in this period of life, medical and psychosocial advantages and disadvantages of the single mode need to be taken into consideration. DISCUSSION: Continuous ambulatory peritoneal dialysis (CAPD) is the predominant mode of therapy for elderly patients. Medical advantages of CAPD in elderly patients are easier control of hypertension and anemia, slower and sustained ultrafiltration, avoidance of cardiac arrhythmias, improvement of nutritional status, better correction of cognitive functions. Psychosocial benefits are home dialysis program, improvement of quality of life and avoidance of co-morbid diseases. There are contraindications to peritoneal dialysis which apply to elderly as well as to younger patients: inadequate peritoneal membrane function, hernias that cannot be repaired, inability to insert a chronic peritoneal access. Relative contraindications include recurrent pancreatitis, chronic back pain, recent aortic prosthesis placement, severe periferal vascular disease and recurrent diverticulitis. Further potential disadvantages of peritoneal dialysis in the elderly are depression and physical and intellectual incapability of self-performing dialysis in the absence of an adequate assistant. Besides, pain, malnutrition and in-hospitalization time associated with peritonitis may be less well tolerated in the elderly than in younger patients. Finally, anorexia, nausea and protein losses in dialysate may aggravate malnutrition. Food intake in the elderly is lower than in younger patients because of the financial situation, loneliness, habits, inertia, depression, bad teeth, impairment of sense of smell and taste, nausea, impeded moving, use of a variety of drugs and many other reasons. Renal failure aggravates malnutrition in the elderly, while peritoneal dialysis is characterized by significant protein losses in the dialysate. It is advisable to make an individual plan of nutrition for elderly patients on peritoneal dialysis in order to provide adequate intake of proteins, energy, vitamins and minerals. Survival rates are the same in patients on peritoneal dialysis and on hemodialysis, but the number of co-morbid conditions is higher in the first group. Age of course is a major death risk factor. Many complications of peritoneal dialysis occur no more frequently in the elderly than in younger patients. The rate of hospitalization is higher and its duration is longer in elderly patients, due to higher incidence of Staphyloccocus epidermidis peritonitis and vascular disease. Urea removal normalized to urea volume of distribution (Kt/Vurea) and weekly creatinine clearance are used as methods of assessing adequacy of peritoneal dialysis in the elderly. Creatinine production declines significantly in older patients and serum creatinine is a poor measure of level of renal function or dialysis adequacy. Assessment of quality of life is quite subjective. Only 15-30% of elderly patients on peritoneal dialysis relate their health worse t

Age Factors↗

PubMedDate not supplied

[Prostacyclin and pentoxifylline in the treatment of patients with inoperable occlusions of the peripheral arteries of the lower extremities].

INTRODUCTION: The treatment of inoperable patients in terminal stages of chronic arterial occlusive disease is difficult and associated with high incidence of limb amputations and lethal outcomes [1]. Prostacyclin (Pgl2) is a strong vasodilator and the most potent endogenous platelet aggregation inhibitor in men [1-6]. Application of Pgl2 in such conditions is justifiable since it represents the exogenous substitution therapy [7, 8]. MATERIAL AND METHODS: An open blind study included 80 patients with inoperable peripheral arterial occlusion (Fontens stages III and IV) who were divided in two groups: Prostacyclin (PG) and Pentoxyfillyne (CG). Clinical characteristics of the groups were comparable (Table 1). Diagnosis of unreconstructable state was based on clinical and arteriographic results. Prostacyclin in the form of Epoprostenol sodium (Flolan) was used in doses of 5 ng/kg/h of continuous intravenous infusions during 24 h (9), 48 h (21) and 72 h (12). Pentoxyfillyne was also administered in continuous intravenous infusions during 24 h (2), 48 h (3) and 72 h (33) in daily dose of 300 mg. Duration of treatment was based on the subjective condition of the patients, i.e., when the patient reported the improvement the therapy was discontinued. Following the completion of infusion therapy, medicamentous therapy was initiated in all patients (Pentoxyfillyne 3 x 400 mg, Aspirin 100 mg). Routine laboratory tests (RBC, haemoglobin, haematocrit, platelet count, WBC, urea, glycaemia, Na, K, lipids, cholesterol, triglycerides), platelet aggregation (Collagen 60 mg/ml; ADP 1.5 mM/ml; RI-PA 1.5 mg/mL), BP, ABI (Doppler) indices and claudication distance were evaluated in all patients after day 1, 7 and 90 following the end of the therapy. RESULTS: The infusion treatment led to subjective reduction or elimination of pain in 52 (32 PG, 20 CG) patients during the immediate course (up to 7 days). The therapy induced no significant changes in laboratory findings, platelet count and BP during the whole follow-up period. Significant decrease in platelet aggregation was recorded 24 hours and 7 days after the initiation of the study only in PG group, while after 3 months no significant decrease in aggregation was found (Table 2). Doppler index changes in both groups were not significant. Significant improvement in claudication distance was recorded 3 months after the infusion therapy: in PG for distance under 100 m (15 patients) and more than 100 m (17 patients), in CG for distance under 100 m (22 pts). In the course of infusion therapy the following complications were recorded: blushing (3 PG), tachycardia (2 PG, 1 CG) and nausea and vomiting (1 PG, 2 CG). Deceleration or temporary discontinuation of infusion led to the improvement of condition, and thus none of the patients was withdrawn from the study. Over a three-month follow-up period 4 lethal outcomes were recorded (2 PG, 2 CG). Causes of death (diabetic nephrosclerosis and renal insufficiency, septic endocarditis, heart insufficiency, CVI) could not have been related to infusion therapy. Due to the progression of gangrene, extremity amputation on different levels was performed in 27 patients (12 PG, 15 CG) of which 15 (7 PG and 8 CG) were performed during the immediate 7-day period while the other amputations were carried out 8-90 days after the treatment. DISCUSSION: The use of prostacyclin leads to temporary and limited distant improvement in arterial flow in patients with occlusive diseases [1]. During the immediate course these effects are manifested by complete absence of pain at rest and initial demarcation of the gangrenous process [1, 4]. Doppler index values established in our series suggest that prostacyclin does not reduce vascular resistance in the major blood vessels; however, it expresses potent vasodilation, antiaggregation and disaggregation effects at the level of microcirculation flow [6, 7]. (ABSTRACT TRUNCATED)

Arterial Occlusive Diseases↗

PubMed2000

Long-term followup of elderly donors in a live related renal transplant program.

PURPOSE: It is a concern that elderly donors may have increased risks in the perioperative period due to age related changes in various organ systems. Nephrosclerosis, atherosclerosis and low glomerular filtration rate may portend a poor graft outcome. We performed a study to determine function and outcome of kidneys from elderly donors. MATERIALS AND METHODS: A retrospective analysis of our live related transplant program from November 1989 to December 1998 revealed that 112 donors were older than 55 years (range 55 to 81). Of the recipients of these kidneys from elderly donors 98 had a followup of more than 2 years (group 1), and they were compared to a cohort of 87 patients whose kidney donors were younger than 45 years (group 2). Allograft function was evaluated by serum creatinine and differential glomerular filtration rate was determined by (99m)technetium diethylenetriamine pentaacetic acid renal scan. All donors were followed regularly. RESULTS: Mean donor age plus or minus standard deviation was 57.4 +/- 4.3 and 31.4 +/- 7.6 years in groups 1 and 2, respectively. Mean followup plus or minus standard deviation was 42.44 +/- 20.46 months in group 1 and 40.04 +/- 27.28 months in group 2. The 1-year graft survival rate was 91.84% and 88. 51%, and the 5-year graft survival rate was 72.72% and 75.13% in groups 1 and 2, respectively. Serum creatinine was 1.5 +/- 0.65 and 1.7 +/- 1.52 mg./dl. in group 1 and 1.4 +/- 0.55 and 1.5 +/- 1.41 mg. /dl. in group 2 at 1 year and last followup, respectively. Glomerular filtration rate was 37.2 +/- 11.2 and 37.3 +/- 10.7 ml. per minute in group 1 and it was 45.3 +/- 8.6 and 47.7 +/- 11.3 ml. per minute in group 2 at 1 year and last followup, respectively. Acute rejection rate was significantly higher in group 1 (42%) compared to group 2 (19%). Both groups were comparable in terms of infectious episodes, antihypertensive requirement and incidence of acute tubular necrosis. There was no added morbidity for elderly compared to younger donors. CONCLUSIONS: In view of acute donor shortage and if properly screened, elderly kidneys can be used without increasing the risk to donor or compromising graft outcome.

Adult↗

PubMed1999

Emerging concepts in antihypertensive therapy: the benefits of angiotensin II blockade.

Essential hypertension affects more than 40 million Americans, or one in four adults. The prevalence of hypertension is greater among the African-American population, with a distressingly high rate of end-organ complications. Although diabetes mellitus has surpassed hyper tension as the dominant etiology of end-stage renal disease in the United States, kidney failure secondary to hypertensive nephrosclerosis remains a significant problem, particularly among African Americans. During the past decade, a shift in the paradigm for the renin-angiotensin system (RAS) has evolved from a circulating vasoactive cascade toward angiotensin II (ANG II) formation at the cellular level. The molecular components of the RAS have been identified in cells, documenting the existence of an autocrine tissue RAS, as well as the presence of enzymes, which catalyze the formation of ANG II by angiotensin-converting-enzyme-independent pathways, providing new targets for therapeutic intervention. The latter challenge has important clinical implications, in view of recent evidence implicating ANG II in pathologic cell growth and cell death and fundamental events in the remodeling of the vascular wall and myocardium in the setting of hypertension. This review focuses on ANG II as a major determinant of end-organ damage in essential hypertension; the benefits of ANG II blockade at the end-organ level, which appear to be independent of the blood pressure-lowering effect; and the emerging role for ANG II receptor antagonists as first-line agents in the treatment of essential hypertension.

Adult↗

PubMed2000

[Progressive renal failure. Why blood pressure must now be monitored].

Hypertension alone can lead to chronic nephrosclerosis and in addition promote the progressive worsening of renal function in various forms of renal disease, such as diabetic nephropathy, glomerular nephritis or interstitial nephritis. Thus, the treatment of chronic renal disease associated with reduced excretory function, requires not only general measures and a low-protein diet, but also intensified anti-hypertension treatment with diuretics or beta blockers. In a number of studies, progression or renal insufficiency has been shown to be slowed in particular through the use of angiotensin-converting enzyme inhibitors in patients with chronic renal failure.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed2000

Experimental reproduction of itai-itai disease, a chronic cadmium poisoning of humans, in rats and monkeys.

To establish a useful animal model of Itai-Itai disease (IID) of humans, we conducted the following experiments. Experiment 1: Toxic effects of Cd were compared between ovariectomized (OX) and non-OX rats after daily, intravenous injection of cadmium (Cd) chloride for 14 days. In this experiment, we demonstrated that OX rats were more susceptible to Cd-induced nephrotoxicity and hepatotoxicity than non-OX rats. Experiment 2: OX rats were injected with Cd at doses of 1.0 and 2.0 mg/kg, 5 days a week, for 13 weeks. The bone Cd content was gradually increased for 13 weeks in a dose-dependent manner. Calcium and phosphorus contents in the bone and serum levels of parathyroid hormone and osteocalcin were not significantly different between Cd-treated and control rats. Mild osteomalacic lesions in the cortical bones of the midshaft haversian canals as well as chronic nephropathy appeared in the rats of the 2.0 mg/kg group. Experiment 3: OX rats were treated with Cd at doses of 0.5 and 0.05 mg/kg for 70 weeks. The rats of the 0.05 mg/kg group showed slight anemia and mild degeneration of tubular epithelium after 50 weeks of treatment. In the 0.5 mg/kg group, the rats showed definite osteomalacia of bones and nephrosclerosis. The Cd concentration in the bones increased for the first 25 weeks, but was replaced gradually with iron at from 50 to 70 weeks of the administration period. Iron deficiency anemia appeared in the 0.5 mg/kg group at from 12 to 25 weeks, and changed to renal anemia after 50 weeks of administration. The anemia at 50 and 70 weeks was normocytic and normochromic, and serum erythropoietin levels were not elevated in response to the decrease of hemoglobin concentrations of red blood cells. Experiment 4: Ten, OX cynomolgus monkeys were given intravenous injections of 0, 1.0 or 2.5 mg/kg/day Cd, 2 or 3 days per week, for 13 to 15 months. Normocytic and normochromic anemia, renal lesions characterized by tubular atrophy and interstitial fibrosis (Cd nephropathy), and bone lesions characterized by an increase of osteoid and osteopenia (Cd osteopathy) were induced in the monkeys treated with Cd. These results demonstrated that chronic cadmium toxicosis similar to IID of humans was reproducible in rats and monkeys by repeated intravenous injection of Cd and that a disease entity closely resembling IID of humans could be induced in experimental animals by chronic Cd toxicosis without participation of malnutrition, vitamin D deficiency, impaired absorption at the intestinal mucosa or multiparous birth.

Animals↗