Predictive value of echocardiography and its relation to Kt/V and anthropometric parameters in hemodialysis patients.

BACKGROUND: In order to evaluate the predictive value of echocardiograph parameters for mortality of hemodialysis patients and their relation to Kt/V and anthropometry, a prospective, single center study was analyzed post-hoc. METHODS: This analysis encompassed 106 patients on maintenance hemodialysis monitored for 108 months from 1996 to 2004. spKt/V was calculated using the Daugirdas formula. Anthropometric measurements included mid-arm muscle measurements (MAMC) and percentage of body fat (%fat). Echocardiography included the estimations of left ventricular wall thickness, dimensions and volumes (EDV, ESV), systolic LV function (ejection fraction - EFLV, fractional shortening - VCF, stroke volume - SV) and diastolic LV function (E/A, VTI-A wave of transmitral flow velocity), left atrial diameter, as well as assessment of clinical and biochemical parameters. The Cox proportional hazard model was used to estimate predictive values of echocardiograph parameters. RESULTS: Kt/V correlated significantly with left ventricular systolic and diastolic volumes and function, septal and posterior wall thickness and left atrium dimension. MAMC and %fat also correlated with many echocardiograph parameters. Multivariate Cox regression selected age [HR 1.07; CI (1.03-1.12); p < 0.01], albumin [HR 0.88; CI (0.79-0.97); p < 0.05] and left atrium dimension - binary [values > 4 cm were marked as "1" and others "0" - HR 3.76; CI (1.56-9.03); p < 0.01] as independent predictors of death. CONCLUSION: Left atrium dimension was the most important predictor of mortality among the echocardiograph parameters. Many of these parameters were related to Kt/V and anthropometric measurements and could be the combined consequence of hypervolemia and hypertension.

Inflammatory markers as mortality predictors in continuous ambulatory peritoneal dialysis patients.

BACKGROUND/AIM: Besides peritonitis, the most common complication, indicators of chronic inflammation are also present in patients treated by peritoneal dialysis. The aim of this study was to analyze the predictive value of inflammatory parameters on mortality of continuous ambulatory peritoneal dialysis (CAPD) patients. METHODS: Eighty-seven patients (57 males), aged from 30 to 85 [62.92 (10.61)] years who had been treated by a chronic program of CAPD for 3-113 months were analyzed. The basal period lasted 3 months with a follow-up of 30 months. Clinical parameters, dialysis adequacy and laboratory parameters including some inflammatory markers: serum amyloid-A (SAA), high sensitive C-reactive protein (hs-CRP), fibrinogen, erythrocyte sedimentation rate (ESR) and leukocytes were determined for each patient. Cox regression analysis selected the parameters of univariate and multivariate survival analysis. RESULTS: During the follow-up period, 37 patients (42.5%) died. Univariate analysis selected the following potential mortality predictors (p<0.10): age, months on CAPD, residual urine output, presence of cerebrovascular insult (CVI), KT/V, serum urea and albumin concentrations, SAA, hs-CRP, fibrinogen and ESR. In the multivariate survival analysis four models were created, each with a single inflammatory parameter. In all of these models, besides the age and CVI, inflammatory parameters were the most significant mortality predictors. When the inflammatory markers were analyzed altogether, multivariate analysis established that independent mortality predictors in this group of patients were: SAA, age and CVI. CONCLUSION: It may be concluded that in this studied group treated by CAPD, SAA was the most significant independent mortality predictor among the analyzed inflammatory markers.

A comparison of markers of myocardial injury and their relation to nutritional parameters in hemodialysis patients.

BACKGROUND: Serum cardiac troponin T (cTnT) is a valuable marker of ischemic heart disease (IHD) and left ventricular hypertrophy, as well as a mortality predictor in hemodialysis populations. We compared the value of cTnT, creatinine kinase (CK)-MB mass and myoglobin as mortality predictors in our hemodialysis patients and evaluated their relation to nutritional status. METHODS: A total of 118 hemodialysis patients were prospectively studied from January 2004 to April 2013. Clinical and laboratory evaluations during the 12-month baseline period included the history of IHD, signs of left ventricular hypertrophy (LVH), Kt/V and serum cardiac markers together with the percentage of body fat (%fat), mid-arm circumference (MAC), mid-arm muscle circumference (MAMC), triceps skinfold (TSF) and BMI. RESULTS: Underweight patients had significantly higher cTnT values (Mann-Whitney, p<0.05). Correlation analysis (Spearman) showed an inverse association between cTnT and TSF (ρ=-0.22, p<0.05), as well as between CK-MB mass and TSF (ρ=-0.26, p<0.01). In men cTnT also correlated inversely with %fat (ρ=-0.27, p<0.05) and BMI (ρ=-0.33, p<0.05). In addition, myoglobin was correlated significantly with MAC, MAMC and albumin. Among cardiac markers cTnT was the only independent variable predicting mortality (Multivariate Cox regression, HR=1.04 CI (1.01-1.07); p<0.01; measurement units 0.01 µg/L). CONCLUSION: Troponin T and CK-MB mass were significantly elevated in the underweight patient group. Troponin T was the only independent cardiac marker predictor of all cause mortality in our hemodialysis patients.

Correlation of bone alkaline phosphatase and iPTH with some basic biochemical markers in predialysis and dialysis patients.

BACKGROUND: Bone alkaline phosphatase (BALP) is a direct and independent indicator of impaired bone turnover. We intended to find out whether there are any significant changes in BALP and iPTH levels, in comparison to total Ca, total Mg, inorganic P, total alkaline phosphatase (ALP), and tartrate resistant acid phosphatase (TRAP) in predialysis and dialysis patients. METHODS: Out of 266 patients investigated, 114 were on continuous ambulatory peritoneal dialysis, 112 were on maintenance haemodialysis, while 40 predialysis patients had end stage renal disease. The parameters were analysed according to the manufacturers' instructions. RESULTS: Correlations were established for the bone marker concentrations analysed among the studied groups. The largest ranges were determined for BALP and iPTH. Predialysis and dialysis patients showed very low levels of BALP. Dialysis patients had lower levels of iPTH (p < 0.001), while in predialysis patients the levels were significantly higher (p < 0.05) than recommended for low bone turnover, according to K/DOQI. CONCLUSIONS: The observations made in this study identify BALP as a good indicator of decreased bone turnover in predialysis and dialysis patients. However, in order to reveal a difference between bone activity and the level of parathyroid activity and its effect on bone turnover, it is always necessary to observe both BALP and iPTH levels.

Polyneuropathy in diabetic and nondiabetic patients on CAPD: is there an association with HRQOL?

BACKGROUND: It is well known that patients with uremia, as well as patients with diabetes mellitus, develop polyneuropathy. OBJECTIVES: The signs of polyneuropathy in diabetic and nondiabetic patients on continuous ambulatory peritoneal dialysis (CAPD) and their relation with age, duration of dialysis, biochemical parameters, dialysis adequacy, and health-related quality of life (HRQOL) were analyzed in the present study. PATIENTS AND METHODS: 65 CAPD patients (37 men, age 29-85 years, duration on dialysis 3 months to 14 years) were divided into two groups: group 1 was comprised of 20 diabetic patients (mean age 50.1+/-13.2 years); group 2 was comprised of 45 nondiabetic patients (mean age 62.3+/-9.7 years). Biochemical parameters, dialysis adequacy, and clinical signs were determined. Motor conduction velocity on the peroneal and tibial nerves and sensitive conduction velocity on the sural nerve were measured. The Kidney Disease Quality of Life Short Form (KDQOL-SF) was used to measure the CAPD patients' self-assessment of functioning and well-being using 4 component scores: physical component summary (PCS), mental component summary (MCS), kidney disease target issues, and patient satisfaction. RESULTS: Subjective symptoms were more intense in the diabetic patients and correlated with changes in peroneal and tibial distal motor latency (DML). Diabetic patients were significantly younger, had lower creatinine and higher glucose levels, and all analyzed pathological neurophysiological parameters were higher. Nondiabetic patients had prolonged latency of the F-wave on the peroneal nerve and the tibial nerve and reduced sensitive conduction velocity on the sural nerve. Significant correlations were found between the analyzed neurophysiological parameters and duration of dialysis and diabetes, glucose concentration, and dialysis adequacy in diabetic patients, and between neurophysiological parameters and age and dialysis adequacy in nondiabetic patients. Analysis of the 4 component scores of the KDQOL-SF revealed that diabetic patients had significantly better scores for PCS and MCS, which can be explained by their younger age. Patient satisfaction was worse in diabetic patients and correlated with duration of diabetes. In addition, significant correlations were established between PCS, MCS, and tibial DML (late neuropathic changes) in diabetic patients, and between MCS and tibial F-wave (early neuropathic changes) in nondiabetic patients. CONCLUSION: Polyneuropathy was significantly worse in diabetic than in nondiabetic patients on CAPD. DML on the tibial nerve correlated with glucose concentration, dialysis adequacy, PCS, and MCS in diabetic patients, whereas in nondiabetic patients, dialysis adequacy and azotemia correlated with F-waves on the peroneal nerve and the tibial nerve but MCS only with F-wave on the tibial nerve.

Could the level of serum albumin be a method for assessing malnutrition in hemodialysis patients?

BACKGROUND: Traditionally, serum albumin concentration has been used for assessing the nutrition status of hemodialysis patients despite evidence that the level is also affected by inflammation and many other underlying disorders frequently present in these individuals. The authors evaluated albumin as a nutrition parameter, comparing it with more specific anthropometric parameters. METHODS: The study included a cohort of 271 patients. The analysis involved data obtained after patients entered the study (1994-2004). Anthropometric measurements included skinfolds, mid-arm circumference, mid-arm muscle circumference, percentage of body fat, body mass index, body height, and dry weight. Kt/V and normalized protein catabolic rate were also determined and laboratory analyses undertaken. RESULTS: Serum albumin was only weakly correlated with mid-arm circumference (r = 0.12), mid-arm muscle circumference (r = 0.15), and fat-free mass (r = 0.12). Common factor analysis of nutrition parameters uncovered latent variables, but serum albumin was not associated strongly with them. The sensitivity of albumin in detecting malnutrition was 24%, with a specificity of 88% and a predictive value of 74%. Graphic analysis showed disagreement in albumin levels with percentage of body fat and mid-arm muscle circumference. CONCLUSION: Serum albumin determination was shown to be a test with low sensitivity and specificity for evaluating malnutrition in hemodialysis patients. The values correlated weakly and showed graphic disagreement with anthropometric parameters. Therefore, methods that measure percentage of body fat and muscle mass should be used together or instead of serum albumin level for assessing the nutrition status of hemodialysis patients.

[Cardiovascular morbidity and mortality risk factors in peritoneal dialysis patients].

Cardiovascular (CVS) morbidity and mortality in the end-stage renal disease (ESRD) patients on peritoneal dialysis therapy is 10-30 folds higher than in general population. The prevalence of well known traditional risk factors such as age, sex, race, arterial hypertension, hyperlipidaemia, diabetes, smoking, physical inactivity is higher in the uraemic patients. Besides these, there are specific, nontraditional risk factors for dialysis patients. Mild inflammation present in peritoneal dialysis (PD) patients which can be confirmed by specific inflammatory markers is the cause of CVS morbidity and mortality in these patients. Hypoalbuminaemia, hyperhomocysteinaemia and a higher level of leptin are important predictors of vascular complications as well as CVS events in the PD patients. Plasma norepinephrine, an indicator of sympathetic activity, is high in the ESRD patients and higher in the PD patients than in the patients on haemodialysis (HD). Therefore, norepinephrine may be a stronger risk factor in the PD patients. The same applies to asymmetric dimethylargine (ADMA), an endogenous inhibitor of nitric oxide synthase, which is an important risk factor of CVS morbidity and mortality 15 % higher in the PD than the HD patients. Hyperphosphataemia, secondary hyperparathyroidism and high calcium x phosphate product have been associated with the progression of the coronary artery calcification and valvular calcifications and predict all-cause CVS mortality in the PD patients. Residual renal function (RRF) declines with time on dialysis but is slower in the PD than the HD patients. RRF decline is associated with the rise of proinflammatory cytokines and the onset of hypervolaemia and hypertension which increase the risk of CVS diseases, mortality in general and CVS mortality. In conclusion, it is very important to establish all CVS risk factors in the PD patients to prevent CVS diseases and CVS mortality in this population.

[Peritoneal dialysis in patients with acute renal failure].

The management of patients with acute renal failure (ARF) is very complex and requires meticulous attention to fluid, acid-base and electrolyte balance as well as the removal of uraemic toxins. Peritoneal dialysis (PD) is an important option for treatment of selected patients with ARF, particularly those who are haemodynamically compromised or have coagulation abnormalities. Due to continuous therapy, its efficacy is the same as on haemodialysis, even better. Advantages of PD in ARF therapy: it is widely available and easy to perform; insertion of PD catheter is relatively easy, PD does not require special staff or expensive equipment, arterial or venous puncture and anticoagulation; dosing is easy; there is no interaction between blood and dialyser and there are no episodes of hypotension like in haemodialysis (HD) patients; acid-base and electrolyte imbalance may be easily and gradually corrected, large amounts of fluid can be removed in haemodynamically unstable patients, which allows parenteral nutrition. PD is less efficient than HD in therapy of acute complications (pulmonary oedema, intoxication or hyperkaliaemia) and is not the therapy of choice in patients with extreme catabolism who require daily HD or some other kind of continuous renal replacement therapy. The absolute indication for acute PD is the need for dialysis and inability to perform any other renal replacement technique. Relative indications for acute PD in adults are the following: haemodynamically unstable patients, the presence of bleeding or haemorrhagic conditions, difficulty in obtaining vascular approach, removal of high molecular weight toxins, heart failure refractory to medical treatment. Absolute contraindications for PD are the following: recent abdominal or cardiothoracic surgery, diaphragmatic peritoneal-pleural connections, faecal or fungal peritonitis. Other contraindications are relative. Accordingly, acute PD is the mode of therapy in some specific patients with ABI, especially patients in intensive care units. Survival of ARF patients is similar in PD and HD patients, so acute PD is very important in their therapy.

[Fungal and tuberculous peritonitis in patients on peritoneal dialysis: characteristics, therapy and outcome].

Peritonitis is a serious clinical complication in patients with terminal chronic renal failure (CRF) on peritoneal dialysis (PD). The incidence of peritonitis varies from center to center, and during the last decade it occurs approximately in one patient during 24-60 therapeutical months, which is the result of good education of patients, but also of employing the new systems for PD. Fungi as well as Mycobacterium tuberculosis are rare causes of peritonitis in patients on PD therapy. The incidence of peritonitis with these two causes varies: 1-15% and 0.7-3%, respectively. The most frequent causes of fungal peritonitis are yeasts (Candida species 70-100%, with most frequent C. parapsilosis), but rarely filamentous fungi such as: Aspergillus, Paecilomyces, Penicillium, Zygomycetes, etc. Gram stains are helpful for diagnosis, as well as the culture of peritoneal effluent. There are various kinds of treatment protocols: withdrawal of peritoneal catheters and application of antimicotic drugs such as amphotericin B (which has recently been abandoned), oral flucytosine, oral or intraperitoneal fluconazole (imidazol) or itraconazol in the case of resistance. Although clinical signs disappear, most of these patients cannot continue with peritoneal dialysis therapy because of peritoneal adhesions, abscesses, fibrosis or progressive sclerosing peritonitis. Percentage of death is 12-44%. The incidence of tuberculosis is higher in patients with CRF in comparison with the entire population, and tuberculous peritonitis can develop in patients who had infection with Mycobacterium tuberculosis which was not treated adequately. Diagnosis can be made by detecting mycobacterium in peritoneal effluent (cultivation for 6 weeks) and/or acidophilic bacillus or typical granuloma in peritoneal biopsy. Therapy consists of removing the peritoneal catheter and long lasting antituberculotic therapy: izoniazid, rifampicin, pyrazinamide, pyridoxin (6-12 months). Streptomycin and ethambutol are to be avoided because of side effects in these patients. In spite of therapy, possible consequences are: ultrafiltration loss, obstruction of intestines because of adhesions, abdominal abscesses, fistulae, ending PD therapy, and even death.

Ten years' experience in subtotal parathyroidectomy of hemodialysis patients.

Secondary hyperparathyroidism (SHP) is a frequent complication of long-term dialysis patients, and surgical parathyroidectomy remains necessary in patients resistant to medical therapy. The present paper reports single center results in subtotal parathyroidectomy, presenting diagnostic procedure, indications for parathyroidectomy, and postoperative course of metabolic and endocrine disorders. Forty-seven patients (25 males and 22 females), aged 25-60 years, regularly hemodialyzed between 3-23 years, have undergone parathyroidectomy at our Clinical Center during the last 10 years. The patients had plasma iPTH levels 8-45 times higher than the top normal limit, high values of alkaline phosphatase, calcemia on the upper normal level, and hyperphosphatemia. Radiographic changes characteristic for SHP were seen in all patients before parathyroidectomy, and the most common were subperiosteal resorptions (100%), bone cysts and periosteal neostosis (66%), and extraskeletal calcifications (98%). Enlarged parathyroid glands were seen by ultrasound in 62% of patients. All patients manifested pruritus and bone pain, 89% of them had myopathy, while other symptoms and signs were present in lower proportions. After parathyroidectomy, pruritus and myopathy reduced significantly, while pain in bones and joints remained. One patient had brown tumor at the maxillary bone that regressed gradually after parathyroidectomy. Significant decreases of phosphate and calcium levels were recorded in all but two patients on the very first postoperative day. Regular peroral and parenteral supplementations of calcium and vitamin D metabolites were used, but calcemia was not normalized until the end of the third week of the postoperative period. Serum alkaline phosphatase showed an increase after the surgery, thereupon a sudden and then slower decrease up to 1 year from the surgery. Plasma iPTH levels, checked on the 21st postoperative day, were close to the lower normal limit in all but two (4.3%) patients with persistent SHP, who required reoperation. In conclusion, subtotal parathyroidectomy was proved as a successful and safe treatment for patients with SHP resistant to medical therapy, and treatment was followed by improvement of clinical symptoms and metabolic disorders.

[Clinical importance of determination of serum amyloid A]. / Klinicki znacaj odredjevanja serum-amiloida A.

Serum amyloid A (SAA) is an acute phase first class protein discovered a quarter of the century ago. Its concentration depends on clinical findings of the patient, illness activity and the therapy applied. SAA increases moderately to markedly (100-1000 mg/l) in bacterial and fungal infections, invasive malignant diseases, tissue injuries in the acute myocardial infarction and autoimmune diseases such as rheumatoid arthritis and vasculitis. Mild elevation (10-100 mg/l) is often seen in viral infections, systemic lupus erythematosus and localized inflammation or tissue injuries in cystitis and cerebral infarction. SAA as sensitive, non-invasive parameter is used in organ transplantation where early and correct diagnosis is needed as well as where prompt therapy is required. Besides acute kidney allograft rejection, SAA is used in the diagnosis of rejection after liver transplantation, simultaneous pancreas and kidney transplantation and also in bone marrow transplantation (acute "graft vs. host disease"). Simultaneous determination of C-reactive protein (CRP) and SAA may point to acute kidney allograft rejection. Standard immunosuppressive therapy with cyclosporine A and prednisolone significantly suppresses the acute phase CRP reaction both in operation itself and acute rejection, but not in infection. On the other hand, SAA rejection in operation, acute allograft rejection and infection is present in spite of cyclosporine A and steroids therapy. Different reaction of SAA and CRP in transplant patients to cyclosporine A therapy helps in differentiation between the infection and rejection. Although CRP and SAA are sensitive and acute phase reactants, their serum concentrations cannot be valued as prognostic and diagnostic criteria without creatinine serum concentration and clinical findings. In addition, they offer important information for clinical diagnosis as well as the kind of therapy.

[Slowing the progression of chronic renal insufficiency with captopril in rats with spontaneous arterial hypertension and adriamycin nephropathy]. / Usporavnje progresije hronicne insuficijencije bubrega kaptoprilom kod pasova sa spontanom arterijskom hipertenzijom i adriamicinskom nefropatijom.

INTRODUCTION: The role of hypertension in chronic renal failure (CRF) progression was described in 1914 by Volhard and Fahr [1], in 1940 by Rite and colleagues [2] and subsequently many studies described the effects of various antihypertensive drugs on regulation of blood pressure and CRF progression. The recent experimental and clinical studies especially emphasized the role of angiotensin converting enzyme (ACE) inhibitors in the regulation of hypertension and slowing down of CRF progression, but there are still issues for discussion and disagreement [2-14]. The aim of this study was to analyse the effects of captopril on clinical, biochemical and morphological changes in spontaneously hypertensive rats (SHR) with adriamycin (ADR) nephropathy. SUBJECTS AND METHODS: Experimental animals. Adult (24 weeks) female spontaneously hypertensive rats (SHR), weighting about 200 g, were bred at the Institute of Medical Research, Belgrade. The rats were randomly divided in the following groups: 1. CONTROL GROUP: 12 SHR; 2. Adriamycin group (ADR): 27 SHR treated with adriamycin (2 mg/kg i.v. twice for 20 days); 3. Adriamycin-captopril group (ADR-C): 30 SHR treated with adriamycin and thereafter with captopril (60 mg/kg/day). Animals were followed-up for 18 weeks after second adriamycin injection. Systolic blood pressure was measured at 2 weeks intervals throughout the study. Blood and urine samples were collected in weeks--4, 6, 12, and 18. Morphologic studies. Rats were killed at weeks 6, 12 or 18 after the second adriamycin injection, when the kidneys were removed and fixed in neutral buffered formalin (10%). Paraffin embedded tissue sections 4 microns thick were stained with hematoxylin and eosin, periodic acid-Schiff reagent (PAS), Thrichrom Masson and Silver methanamin (Jones) for light microscopic study. A semiquantitative score was used to evaluate glomerular, vascular and tubulointerstitial changes. A minimum of 60 glomeruli for each kidney were examined, and the severity of the lesions was graduated according to the percentage of glomerular sclerosis from 0 to 10 (0--0%; 2--20%; 5--20-50%; 10--100%) [16]. Vascular changes were graduated from 0 to 3 according to hyalinosis in the walls of the artenoles (1--0%; 2--< 50%; 3--50-100%; 4--100%) [17]. Tubulointerstitial changes were semiquantitatively expressed by calculation of separately the index of interstitial fibrosis (0--0%; 2--< 20%; 5--> 20%; IQ--> 40%) and the index of interstitial infiltration and tubular atrophy (0--0%; 1--< 20%; 2--> 20%; 3--> 40% [18]. Results were presented as mean +/- SD. Differences between groups in functional data as well as morphologic lesions were studied by one-way analysis of variance and the unpaired T-test. RESULTS: Captopril decreased systemic blood pressure in ADR SHR significantly, but failed to prevent proteinuria (Fig. 1). Urea and creatinine in serum progressively increased in all studied groups, but faster in ADR SHR groups than in controls (Table 1). Creatinine clearance decreased faster in ADR group than in ADR-C group, but without statistical significance (Table 1). Among sixty nine analysed rats at the beginning of the study, sixteen died during the study. The other animals (Table 1) were killed at weeks 6, 12 and 18; pathohistological changes of their kidneys with glomerular, vascular and tubulomterstial indexes are presented in Table 2. In control group of rats minimal glomerular and interstitial changes could be seen in week 18, mild tubular changes were present in weeks 12 and 18, and marked changes in blood vessels were manifested in week 12, as well as in week 18 (Fig. 2, Table 2), when their statistical significance was higher than in rats treated with adriamycin. Glomerular, tubular and interstitial changes were mostly pronounced in adriamycin treated rats and became more expressive during the experiment (Table 2, Fig. 3). In ADR-C group of rats captopril slowed down glomerular changes, but significantly in week 18 only (Table 2). The same was with interstitial changes (Table 2, Figs. 3-c, 4-c). Tubular and vascular changes were less in week 6 in ADR-C group than in ADR group, what was leveled off later in the study (weeks 12 and 18) (Table 2). DISCUSSION: Although Richard Bright was probably the first person to notice that severe renal diseases were associated with changes of the cardiovascular system, Volhard and Farhr first described that high blood pressure was the major cause of progressive loss of renal function in chronic renal diseases [1]. Subsequently, many authors in their experimental and clinical studies described the effects of various antihypertensive drugs on regulation of blood pressure and slowing down of CRF progression. Various experimental models were used in their studies [8, 19-21]. With discovery of ACE inhibitors and first studies which pointed that this group of drugs effectively slowed down CRF progression, many authors studied their effects on systemic blood pressure regulation, reduction of glomerular hypertension and slowing down of CRF progression. Anderson, Rennke and Brenner studied the effects of "triple therapy" (reserpine, hydralazine and hydrochlorotiazide) and ACE inhibitor enalapril in rats with subtotal nephrectomy [3]. Enalapril decreased systemic blood pressure, glomerular hypertension, proteinuria and glomerular sclerosis [9, 22-24], while "triple therapy" reduced only systemic hypertension with no effect on glomerular hypertension and glomerular damage [25]. The same was described in uninephrectomised DOCA rats [26]. Raij and colleagues also described better effects of enalapril in relation to "triple therapy": enalapril reduced mesangial expansion and proteinuria [27]. Our study [8] as well as that of other authors [3, 25, 26] agree that ACE inhibitor captopril was better in comparison with hydralazine in slowing down glomerular sclerosis and mesangial expansion inspite of good regulation of blood pressure with both drugs. In ADR SHR, ACE inhibitors reduced proteinuria [6, 10, 20, 25], regulated systemic blood pressure (Fig. 1-a), decreased glomerular hypertension and glomerular sclerosis [7, 10, 25, 28, 29] which were also found in our experimental study (Fig. 1, Table 2). These were confirmed in clinical studies too: first, in patients with diabetic nephropathy [30] and later in patients with nondiabetic kidney diseases [6, 30-34]. In SHRs blood pressure increased from week 4 to 10, and after week 12 blood pressure was stabilized on a constantly higher level [36]. Our studied rats were 24 weeks old at the beginning of the study and they had stable hypertension in that period (Fig. 1-a). With the age in SHRs renal function aggravated very slowly, with little changes in glomeruli, higher in tubuloniterstitium [19] and the highest in blood vessels. SHRs developed glomerular changes very late inspite of hypertension, because glomeruli were protected with preglomerular vasoconstriction [37]. These mild changes described by various authors could be also seen in our study (Fig. 2, Table 2). Pathohistological changes in rat kidneys caused with anthracycline were first described by Stenberg and Phillips in 1967 [41]. Adriamycin (doxorubicin hydrochloride) induced syndrome nephroticum. Light microscopic study revealed no changes at the beginning of the study, but later (7-9 months) glomerular sclerosis, tubular dilatation and interstitial fibrosis developed which led to chronic renal failure [42, 43], (Fig. 3). Therapy with ACE inhibitor, captopril, in rats with adriamycin nephropathy lowered glomerular sclerosis [7, 12, 25, 28, 29], and mesangial expansion was very rare. In our earlier studies, captopril was found to decrease glomerular sclerosis in the early phase of adriamycin nephropathy in SHRs [8, 29], what was also confirmed in this study: captopril decreased glomerular and tubulointerstitial changes in weeks 6, 12 and 18 after second adriamycin injection, but had no effect on vascular changes (Fig. 4, Table 2). Favorable effects of captopril on tubulointerstiatial changes (especially interstitial) are very important because many authors have described recently better correlation between tubulointerstitial changes and CRF progression [17, 44-46], in comparison to glomerular changes and CRF. Besides, some authors have confirmed better effects of ACE inhibitors when they were given earlier before glomeruli were damaged [47]. CONCLUSION: In SHRs with ADR nephropathy treatment with captopril normalized systemic blood pressure, and slowed down CRF progression in their early stage. These functional changes correlate with significant slowing of glomerular and interstitial changes.