Application of artificial neural networks in estimating predictive factors and therapeutic efficacy in idiopathic membranous nephropathy.

Idiopathic membranous nephropathy (IMN) is one of the most frequent causes of the nephrotic syndrome in adults and one of the most common cause of chronic renal failure among primary glomerular diseases. The aim of this study was to develop artificial neural networks (ANN) to investigate factors of poor outcome for IMN and to evaluate the efficacy of different therapeutic protocols. Data were collected retrospectively for 124 patients with IMN (82 males, mean based on the received therapy patients were divided into three groups: corticosteroids only (group 1), cyclophsophamide with corticosteroids (group 2), and so called Ponticelli protocol (group 3). After achieving satisfactory truthfulness of the transcription function of ANN through clustering, we have applied the efficacy analysis to all patients and then compared them to each group separately, and evaluated the influence of initial characteristics on disease outcome as well as the therapy efficacy. The greatest therapy inefficiency was recorded for isolated corticosteroid therapy (29.41%) and the smallest inefficiency for Ponticelli protocol, for which the greatest accuracy of prognosis was recorded (82.09%). The greatest negative prognostic influence had kidney insufficiency (22%), quantitative proteinuria (15%) and index of interstitial infiltration (14%). Based on our results, we can recommend that patients diagnosed with IMN with renal insufficiency, nephrotic syndrome or a high degree of interstitial infiltration at the time of diagnosis should be treated concomitantly with cytotoxic drugs and corticosteroids, particularly with the Ponticelli protocol.

Relation between serum urea and mortality of hemodialysis patients.

BACKGROUND: It is well known that serum urea concentration is not a good predictor of mortality in hemodialysis patients. On the other hand, urea kinetic modeling has been very successfully used to measure dialysis dose by the Kt/V index, which was found to be a good predictor of mortality. Could there be a relation between urea and mortality, but in some more complex way? METHODS: This is a post-hoc analysis of a single center observation study that included 242 patients and an 11-year observation period. Mortality rates between the quartiles of serum urea levels were examined by a 2 x 4 table with the chi(2) test. Both univariate and multivariate survival analyses were performed with standard and segmented extended Cox regression. RESULTS: The relation between mean urea in the baseline period and mortality showed an irregular U-shaped curve. The lowest mortality was observed in the third quartile (28 to 31 mmol/L). The relation between mean urea in the whole observation period and mortality was a J-shaped curve. The lowest mortality was in the second quartile (25-27 mmol/L). Urea was not a predictor of mortality in the whole cohort, but low-urea (binary) and high-urea (binary) were independent predictors of mortality in the corresponding models using standard or extended Cox regression. CONCLUSION: This study revealed a complex relationship between urea and mortality in hemodialysis patients. Patients with low or high urea levels exhibited higher mortality than those with medium levels, while both low and high levels of urea were independent predictors of all-cause mortality.

Today Balkan endemic nephropathy is a disease of the elderly with a good prognosis.

BACKGROUND: The outcome for Balkan endemic nephropathy (BEN) patients diagnosed in 1992 was analyzed in 2006 with the aim of detecting factors associated with disease progression and patient outcome. METHODS: In 1992 BEN was detected in 119 patients (53 males, 56.9 +/- 13.8 years) from the village of Sopic. Changes in creatinine clearance as well as outcome (death or onset of regular hemodialysis) were analyzed retrospectively in 2006. RESULTS: During the 14-year period 47 patients deceased (5 on hemodialysis) at the mean age of 72.2 +/- 8.2 years, while no data were available for 13 cases. Out of 59 remaining patients 3 were on hemodialysis in 2006 and 56 participated in the control examination. Of these 12 had creatinine clearance at least 50% lower than in 1992 and 44 had unchanged creatinine clearance. Logistic regression revealed age and proteinuria, but linear regression only age as significant prognostic factors for changes in creatinine clearance. The all-cause mortality rate varied between 1.1 and 5.3% per year and was similar to the mortality rate of the general population. The main cause of death was cardiovascular disease (40.5%) followed by malignant diseases (17%), most frequently (11%) due to upper urothelial tumors. Urine protein and age were found to be a significant independent predictor of all-cause mortality. CONCLUSION: In the village of Sopic BEN was commonly detected in patients in their fifties, progressed slowly, but most patients died from other causes at old age before end-stage renal disease occurred. Kidney function remained stable over the decade in three quarters of the surviving patients. Age and proteinuria were found to be prognostic factors for both disease progression and patient mortality.

Hemodialysis modality, percentage of body fat, and patient survival.

BACKGROUND: A number of studies have reported lower mortality of overweight hemodialysis patients. This post hoc analysis of an observational prospective single-center study was aimed at elucidating whether both being overweight and surviving longer could result from changes in the hemodialysis modality. METHODS: The study included a cohort of 242 patients who were gradually switched from cuprophane membrane and acetate dialysis to polysulfone (including high-flux) membranes and bicarbonate dialysis. The analysis involved 12 months of baseline data obtained during the first calendar year after the patients entered the study (1994-2001) and repeated measurements for up to 132 months of follow-up (until 2004). Anthropometric measurements were made during the winter season and the percentage of body fat (%fat) was calculated from triceps, biceps, subscapular, and suprailiac skinfolds (K/DOQI guidelines).Kt/V, normalized protein catabolic rate, and cardiovascular comorbidity were also determined and laboratory analyses undertaken. RESULTS: Significant correlations were found between %fat and bicarbonate dialysate as well as polysulfone membrane and high-flux membrane. The linear mixed model showed dependence of %fat on polysulfone and high-flux membrane (p<0.01) Multivariate Cox regression (time-dependent covariates) found %fat to be an independent factor for longer survival, in addition to polysulfone and high-flux membranes. CONCLUSION: Changes in hemodialysis modality were followed by both higher body fat percentage and patient survival. The reverse epidemiology of overweight patients might be at least partially the result of the influence of nonnutritional factors, such as a change in hemodialysis modality (introducing biocompatible high-flux and low-flux membranes and bicarbonate dialysis).

Could depression be a new branch of MIA syndrome?

The aims of the present study were to determine the prevalence of depression in our dialysis patients, to detect the most powerful variables associated with depression, and to determine the role of depression in prediction of mortality. The prospective follow-up study of 128 patients (77 HD and 51 CAPD, 65 male, aged 53.8 +/- 13.5 years, dialysis duration 64.7 +/- 64.8 months) was carried out over 36 months. Depression by the Beck Depression Inventory-BDI-II score, laboratory parameters (hemoglobin, serum albumin and creatinine concentration), immunological status (cytokines and hsCRP), comorbidity by Index of Physical Impairment (IPI) and adequacy of dialysis by Kt/V were monitored. The overall prevalence of depression in the dialysis patients (BDI score > or = 14) was 45.3%, and 28.2%, respectively, for moderate and severe depression (BDI > or = 20). The most powerful variable associated with depression was IL-6, but associations with albumin, hemoglobin, creatinine and IPI score were also found. During the follow-up period 36 patients died, 7 patients left the cohort and 2 patients were transplanted. If IPI score was not included in the multivariate Cox analysis, the BDI score remained one of the best predictors of mortality along with albumin. In conclusion, because of the close association of depression with inflammation, malnutrition, and cardiovascular mortality, it could be speculated that depression is one branch of the MIA (malnutrition, inflammation, atherosclerosis) syndrome.

Fuzzy role of hyperhomocysteinemia in hemodialysis patients' mortality.

Recent studies give contradictory data regarding the role of hyperhomocysteinemia (hyperHcy) in cardiovascular (CV) morbidity and mortality in hemodialysis (HD) patients. The aims of the present study were to detect the most powerful variables associated with hyperHcy as well as to evaluate the relationship between hyperHcy and CV morbidity and mortality. The prospective follow-up study of 113 patients (52 males, aged 55.2+/-13.1 years) maintained by HD for 81.9+/-56.9 months at our Institute was carried out over 55 months. Fifty-seven (50.4%) of the examined patients were supplemented with water-soluble vitamins including folic acid and vitamin B complex pills or ampoules. Total serum Hcy level was determined by high-performance liquid chromatography, while serum folic acid and vitamin B(12) were measured by radioimmunoassay. The multivariate analysis showed HD duration (r=0.608; P=0.02) and folic acid serum level (r=-0.580; P=0.03) to be significant predictors of serum tHcy concentration. The multivariate Cox regression analysis of CV mortality revealed diabetes mellitus and heart failure as the most powerful positive predictors, while creatinine, albumin and vitamins intake therapy were negative predictors of CV mortality. Long-term supplementation with the usual doses of vitamins is followed with increased survival in hemodialysis patients. Although total serum Hcy level was not found to be a predictor of overall and CV mortality, the role of hyperHcy. as risk factor for CVD cannot be excluded in hemodialysis patients.

Comparative survival analysis of urea kinetic based indices.

BACKGROUND: Although urea kinetic modeling indices for measuring dialysis dose are recommended by world expert groups, it is not quite clear whether some of these are superior in predicting the outcome over others. This prospective, single-center study was carried out with the aim to compare predictive value of different indices and methods of measuring dialysis dose. METHODS: The analysis included 93 anuric patients having been on hemodialysis for at least 2 years who were followed-up for 75-months. The dialysis dose was measured by Kt/V (formal UKM, 3 and 2 urea samples), Kt/V (Daugirdas), Kt/V (Lowrie), eKt/V (Daugirdas), URR and TAC urea. RESULTS: Correlations between dialysis indices and survival time were significant for all indices (p<0.01) except for TAC. All indices, except for TAC urea, were significant predictors of mortality (multivariate Cox regression analysis; p<0.01) and differences of significant levels among these colinear parameters were small. CONCLUSION: All examined indices except for TAC urea were highly predictive of patient mortality. Daugirdas and Lowrie simplified Kt/V indices are as predictive of all-cause mortality as more complex formal UKM methods in long-term patients on a 3x4h/week schedule.

[Radiographic changes in the sella turcica in female patients on chronic hemodialysis]. / Rendgenske promene cele turcike kod bolesnica na hronicnoh hemodijalizi.

The bone disease in chronic renal failure patients with secondary hyperparathyroidism is usually termed renal osteodystrophy. Radiographic methods have been applied in renal bone disease mainly to discover lesions on long bones, hands and fee. During the evaluation of hormonal disturbances of hemodialysed chronic renal failure female patients, roentgenograms of sella turcica were taken. Findings that were detected were most probably the consequences of renal osteodystrophy. Osteoporosis of clinoid processes posteriores and dorsum sellae and intrasellar calcifications were confirmed in 25 percent of investigated patients. Lateral view of the sellae turcica demonstrated a "double floor".These pathological findings in sella turcica region could be of practical importance because of well known anatomophysiological position of this sceletal structure.

[Hemostatic system parameters in patients with chronic renal insufficiency and arteriovenous fistula thrombosis]. / Osnovni parametri hemostatskog sistema kod bolesnika s hronicnom insuficijencijom bubrega i trombozama arterio-venske fistule.

Functional disturbances among different tissues and organic systems are associated with chronic renal failure. The most common problems following the disturbances in complex hemostatic changes in uremic patients are prolonged bleeding time ant the increased thrombosis tendency. As the patients vascular access is critical to the treatment of the chronic haemodialysis patient, we performed an investigation of causes of repeated vascular access thrombosis with purpose of detecting any consistent abnormality of the haemostatic system. Research has been conducted on a group of 29 patients (14 males and 15 females), age 21 to 61 (x = 45), on regular haemodialysis from 1 to 6 years (x = 2.2); 23 of them having one episode of thrombosis of vascular access, and 6 having two episodes. Partial thromboplastin time was among the normal ranges in all investigated subjects, three of them had low prothrombine time and thrombine time was prolonged in two cases. The high fibrinogen value was found in 19 patients. Mean value of platelet count was normal, though seven patients had thrombocytopenia. Absence of coagulum retraction was found in three patients. Assessment of blood coagulation in this study could not explain the development of repeated thrombotic events affecting arterio-vein fistula in chronic renal failure patients receiving haemodialysis. That points out the necessity to analyze functional status of natural coagulation inhibitors, fibrinolytic system and platelet function.

[Monitoring the nutritional status in patients on hemodialysis]. / Pracenje stanja uhranjenosti kod bolesnika na hemodijalizi.

In order to monitor changes of the nutritive status of hemodialyzed patients, antropometric and laboratory parameters of the population of hemodialyzed patients in 1988 vs. 1994 have been compared. Antropometric parameters were measured by the same investigator. The results show absence of significant difference between antropometric parameters (body weight after hemodialysis, body mass index, triceps fold, circumference of upper arm and percentage of fat) in the patients hemodialyzed in 1988. The laboratory parameters (albumin and transferrin), however, show significant increase in the 1994 group. In the group of patients subjected to hemodialysis in 1988 as well, albumin was significantly elevated. Nevertheless, no differences in laboratory parameters in healthy populations of 1988 and 1994 were noted (controls). It was concluded that no significant changes in the nutritive status were present among either the population or the same patients, while elevation of laboratory parameters necessitate further investigation.

[Analysis of data on hemodialyzed patients for the development of a data base]. / Analiza podataka o bolesnicima na hemodijalizi radi razvoja baze podataka.

Needs for state-of-the-art records on haemodialyzed patients implies abandoning of conventional paper work and development of a computer data base on haemodialyzed patients. Thus, data on haemodialyzed patients were analyzed. Since haemodialysis is a specific mode of treatment and differs from out-patient and in-patient management, the records also differ from conventional files and histories. The analysis has shown that the data can be groupedinto two sets: dialysis list and history of a haemodialyzed patient. The list contains the data at the onset of dialysis, and the end of the process, and in hourly intervals. The history contains mainly relatively permanent data (personal data and basal medical parameters), annual (records and primary data) and monthly (dialysis records, history and current condition, laboratory analyses and therapy). Most of the data are systematic, i.e. periodic and necessitate tabular presentation. It has been concluded that due to the tabular presentation and predominance of systematic information, the data base will be superior to conventional records.

[Quantitative approach to dialysis adequacy (part two)]. / Kvantitativni pristup adekvatnosti dijalize (drugi deo).

A quantitative assessment of dialysis and prescription of dialysis as therapy in every single patient have always been a continuous problem. Numerous efforts have been made to date to determine the kind of therapy for patients on hemodialysis on the basis of simple objective indices instead of clinical and laboratory parameters. Some of these indices have been widely accepted nowadays. Although the main clinical and laboratory parameters have still been currently applied in the assessment of peritoneal dialysis adequacy, serious quantitative approaches are made even in these cases regarding the more accurate therapy. The first part of the article deals with the development of quantitative approach to dialysis adequacy in certain models; the second part concerns dialysis prescription based on Gotch's and Sargent's modification of the American National Cooperative Dialysis Study (NCDS) as well as on Direct dialysis quantification (DDQ) and peritoneal dialysis adequacy.

[Quantitative approach to dialysis adequacy (Part one)]. / Kvantitativni pristup adekvatnosti dijalize (prvi deo).

A quantitative assessment of dialysis and prescription of dialysis as therapy in every single patient have always been a continuous problem. Numerous efforts have been made to date to determine the kind of therapy for patients on haemodialysis on the basis of simple objective indices instead of clinical and laboratory parameters. Some of these indices have been widely accepted nowadays. Although the main clinical and laboratory parameters have still been currently applied in the assessment of peritoneal dialysis adequacy, serious quantitative approaches are made even in these cases regarding the more accurate therapy.

Treatment of secondary hyperparathyroidism with intermittent oral high doses of 1-alpha-OHD3 plus pharmacological dose of 24,25(OH)2D3.

The present study examined the effect of intermittent oral high doses of 1-alpha-OHD3 in combination with a pharmacological dose of 24,25(OH)2D3 on parathyroid hormone (PTH) secretion. Twenty hemodialysis (HD) patients (10 males, aged 26-72 years, on regular hemodialysis for 7-128 months) with secondary hyperparathyroidism resistant to long-term low-dose 1-alpha-OHD3 therapy were studied for 24 weeks. At the outset of the study they were randomly divided into two groups: group 1 received high-dose 1-alpha-OHD3 plus 24,25(OH)2D3 (2 x 5 micrograms/day) and group 2 was on monotherapy with 1-alpha-OHD3. 1-alpha-OHD3 was given three times a week in the evening before each HD in gradually increased doses from 1 to 4 micrograms adjusted to keep serum calcium levels below 2.6 mmol/L. During the therapy mean serum calcium and ionized calcium levels increased but remained in the normal ranges without differences between the two groups. However, the frequency of hypercalcemia episodes was different in the two groups. In the first 12 weeks the number of hypercalcemia episodes was significantly lower in group 1 than in group 2 (6 vs. 12; p < .05), allowing the use of significantly higher 1-alpha-OHD3 doses in group 1. In the second 12 weeks of the study the 1-alpha-OHD3 dose in group 1 had to be reduced due to more frequent appearance of hypercalcemia. So, the 1-alpha-OHD3 doses became similar in the two groups during the second 12 weeks of the study.(ABSTRACT TRUNCATED AT 250 WORDS)

[Tables of composition of prepared foods for patients on hemodialysis]. / Tablice sastava pripremljene hrane za bolesnike na hemodijalizi.

Numerous mutually contradictory conditions in diets for haemodialysis patients require knowledge about the composition of prepared food for each individual patient. The aim of this study was to make appropriate tables of prepared food on the basis of the analysis of patients nutrition. A list of the food way of its preparation was formed after dietary interviews. The most frequent food was prepared in the usual way and its composition was computed with food tables. The tables of prepared food composition facilitate the prescription of dietary daily meals, and make the therapy easier.