KAUNAS UNIVERSITY OF MEDICINE
Asta Stankuvienė
SURVIVAL AND ASSOCIATED
RISK FACTORS OF PATIENTS
ON CHRONIC HAEMODIALYSIS
IN LITHUANIA
Summary of Doctoral Dissertation Biomedical Science, Medicine (07 B)
Kaunas, 2010 w w .AB B Y Y.c o m w w .AB B Y Y.c o m
Dissertation was carried out in Kaunas University of Medicine, during 2006– 2010.
Scientific Supervision
Assoc. Prof. Dr. Inga Arūnė Bumblytė (Kaunas University of Medicine, Biomedi-cal Sciences, Medicine – 07 B).
Consultant
Prof. Dr. Ramunė Kalėdienė (Kaunas University of Medicine, Biomedical Sciences, Public Health – 10 B).
The Dissertation will be defended at the Medical Research Council of Kaunas University of Medicine:
Chairman:
Prof. Dr. Žilvinas Padaiga (Kaunas University of Medicine, Biomedical Sciences, Medicine – 07 B, Public Health – 10 B).
Members:
Prof. Dr. Arvydas Laurinavičius (Vilnius University, Biomedical Sciences, Medi-cine – 07 B)
Assoc. Prof. Dr. Daimantas Milonas (Kaunas University of Medicine, Biomedical Sciences, Medicine – 07 B)
Assoc. Prof Dr. Asta Baranauskaitė (Kaunas University of Medicine, Biomedical Sciences, Medicine – 07 B)
Prof. Dr. Boleslaw Rutkowski (Gdansk University of Medicine, Poland, Biomedi-cal Sciences, Medicine – 07 B).
Opponents:
Assoc. Prof. Dr. Aivaras Jonas Matjošaitis (Kaunas University of Medicine, Bio-medical Sciences, Medicine – 07 B)
Dr. Augustina Jankauskienė (Vilnius University, Biomedical Sciences, Medicine – 07 B).
The Dissertation will be defended at the open session of the Medical Research Council in the Symposia hall of the Kaunas University of Medicine on 4 May, 2010, at 12 h.
Address: Eivenių str. 4, LT-50009 Kaunas, Lithuania.
The summary of the dissertation has been sent on 02 April 2010.
The full text of the doctoral dissertation is available in the Library of Kaunas University of Medicine.
Address: Eivenių str. 6, LT-50161 Kaunas, Lithuania.
w w .AB B Y Y.c o
m w
w .AB B Y Y.c o
KAUNO MEDICINOS UNIVERSITETAS
Asta Stankuvienė
PACIENTŲ, SERGANČIŲ GALUTINIU
INKSTŲ NEPAKANKAMUMU
BEI GYDOMŲ HEMODIALIZĖMIS,
IŠGYVENIMAS IR SU JUO SUSIJĘ VEIKSNIAI
Daktaro disertacijos santrauka Biomedicinos mokslai, medicina (07 B)
Kaunas, 2010 w w .AB B Y Y.c o m w w .AB B Y Y.c o m
Disertacija rengta 2006–2010 metais Kauno medicinos universitete.
Mokslinis vadovas
Doc. dr. Inga Arūnė Bumblytė (Kauno medicinos universitetas, biomedicinos mokslai, medicina – 07 B).
Konsultantas
Prof. dr. Ramunė Kalėdienė (Kauno medicinos universitetas, biomedicinos mokslai, visuomenės sveikata – 10 B).
Disertacija ginama Kauno medicinos universiteto medicinos mokslo krypties taryboje:
Pirmininkas
Prof. habil. dr. Žilvinas Padaiga (Kauno medicinos universitetas, biomedicinos mokslai, medicina – 07 B, visuomenės sveikata – 10 B)
Nariai:
Prof. dr. Arvydas Laurinavičius (Vilniaus universitetas, biomedicinos mokslai, me-dicina – 07 B)
Doc. dr. Daimantas Milonas (Kauno medicinos universitetas, biomedicinos moks-lai, medicina – 07 B)
Doc. dr. Asta Baranauskaitė (Kauno medicinos universitetas, biomedicinos moks-lai, medicina – 07 B)
Prof. dr. Boleslaw Rutkowski (Gdansko medicinos universitetas, Lenkija, biomedi-cinos mokslai, medicina – 07 B)
Oponentai:
Doc. dr. Aivaras Jonas Matjošaitis (Kauno medicinos universitetas, biomedicinos mokslai, medicina – 07 B)
Dr. Augustina Jankauskienė (Vilniaus universitetas, biomedicinos mokslai, medici-na – 07 B)
Disertacija bus ginama viešame Medicinos krypties tarybos posėdyje 2010 m. gegu-žės 4 d. 12 val.
Kauno medicinos universiteto Mokomojo laboratorinio korpuso Simpoziumų salėje. Adresas: Eivenių g. 4, LT-50009 Kaunas, Lietuva.
Disertacijos santrauka išsiuntinėta 2010 m. balandžio 2 d.
Disertaciją galima peržiūrėti Kauno medicinos universiteto bibliotekoje. Adresas: Eivenių g. 6, LT-50161 Kaunas, Lietuva.
w w .AB B Y Y.c o
m w
w .AB B Y Y.c o
ABBREVIATIONS
ANZDATA – Australian and New Zealand Dialysis and Transplant Registry
AUC – area under the curve
CORR – Canadian Organ Replacement Registry CRP – C-reactive protein
DOPPS – Dialysis Outcomes and Practice Patterns Study ERA-EDTA – European Renal Association Registry
Registry
ESRD – end stage renal disease
Hb – haemoglobin
HD – haemodialysis
Kt/V – HD adequacy index
K/DOQI – Kidney Disease Outcomes Quality Initiative
n – sample size
PD – peritoneal dialysis PTH – parathyroid hormone r – correlation coefficient
ROC curve – receiver operating characteristic curve
RR – relative risk
RRT – renal replacement therapy USA – United States of America
USRDS – United States Renal Data System Registry 95% CI – 95% confidence interval
INTRODUCTION
End-stage renal disease (ESDR) is highly prevalent worldwide, with more than 1 million patients undergoing renal replacement therapies (RRT), which are a life-saving treatment for such patients. The main factors contributing to the continued growth are the universal ageing of populations, multimorbidity, higher life expectancy of treated ESRD patients and increasing access of patient populations to RRT in countries in which access had previously been limited. Dialysis is still the most common treatment, partly due to insufficient kidney donation to meet the demand for renal transplants. At the end of 2004, 1 783 000 people worldwide were undergoing treatment for ESRD; 1 371 000 (i.e. 77%)
w w .AB B Y Y.c o
m w
w .AB B Y Y.c o
were on dialysis treatment. Analysis of the type of treatment received by dialysis revealed that haemodialysis (HD) remains the most common treatment modality in all regions of the world. At the end of 2004, 89% of patients worldwide were treated by HD and 11% were undergoing peritoneal dialysis (PD) treatment [Grassman et al. 2005].
In most countries, renal registries are responsible for ESRD data collection, analysis and reporting. The most important factor for the renal registries, which influences the collection of annual data, is the response rate to the questionnaire. In some registries, the submission of the data is mandatory and linked to the reimbursement of treatments performed in dialysis facilities. For example, in the United States, the Medicare only reimburses the cost of dialysis treatment after it receives patient data, which are then supplied to the USRDS. Other registries work based on voluntary submission of data. In such cases, only a few renal registries, such as the ANZDATA registry, CORR and the Japanese Society for Dialysis Therapy, receive data from more than 90% of all dialysis facili-ties. Other voluntary national and international registries have a response rate to the questionnaire of the dialysis centres lower than 90%. For these reasons, some registries are an under-representation of patients receiving RRT. Not all renal registries include patients from the first day on RRT; in the USRDS registry, all ESRD patients treated with RRT are included from the 91st day because the Medicare system does not achieve complete reporting of patients’ data before day 90. Thus, patients who die before this time (early mortality within 90 days) are not accounted for by the USRDS. Other registries include patients only on dialysis (the registry of the Japanese Society for Dialysis Therapy) [Schena 2000]. A multicountry European database is organised by the ERA-EDTA, which now consolida-tes renal replacement information from different renal registries collecting patient data of 30 countries. An alternative approach to reporting interna-tional ESRD-relevant data is pursued in the Dialysis Outcomes and Practice Patterns Study (DOPPS). It was initiated in 2002 as an observatio-nal study and presently collects information on haemodialysis practice patterns and their associated outcomes from 12 countries in Europe, North America and Asia. The Fresenius Medical Care, the largest dialysis care company worldwide, uses its international network for retrieving and com-paring ESRD demographic information from 122 countries that have a combined population of 5.9 billion and represent 92% of the total world population. w w .AB B Y Y.c o m w w .AB B Y Y.c o m
There is no renal registry in Lithuania. Until 1990, haemodialysis ser-vices in Lithuania were underdeveloped, but after the restoration of Lithuanian’s Independence, development of HD services has started. However, up to the end of 1996, no precise data about HD services in Lithuania were available, and the main characteristics of HD patients were not known. Even the exact number of HD patients was uncertain. In 1996, the Clinic of Nephrology of Kaunas University of Medicine headed by Prof. Kuzminskis started to collect data about HD services and HD patients in our country. All HD centres were visited annually, and the data on the number of patients and HD stations, demographic characteristics, the main aetiology of ESRD, the duration of HD (hours per week), the type of HD, the drugs used, predialysis blood tests, single-pool Kt/V and the prevalence of hepatitis B and C were collected. For estimation of inciden-ce, information about all patients who started HD in the exploratory year, including those who were transplanted, died or transferred to peritoneal dialysis, was collected. An annual presentation of this observational study results to Lithuanian nephrologists helped to improve quality of HD pa-tients’ care in our country.
On the other hand, this voluntary observational study was cross-sectio-nal in its design. It investigated incidence, prevalence, mortality and care quality of HD patients in Lithuania. Nevertheless, the survival of such patients, one of the most important outcome measures, has never been investigated in Lithuania.
Outcome research is a rapidly evolving field that incorporates epidemio-logy, health service research, health economics and psychometrics. The outcome measures, listed by Epstein and Sherwood, are grouped into three important areas: clinical, characterized by clinical events, physiologic and metabolic measures and mortality; economic, including direct and indirect medical measures; and humanistic, in which symptoms, quality of life, functional status and patient satisfaction are included [Epstein and Sherwood, 1996]. The choice of outcome measures depends on the prio-rities of those examining the data. Clinicians are more interested in clinical and humanistic outcomes whereas patients may be preferentially interested in humanistic measures. Health plan administrators are more interested in economic ones.
Survival of patients on RRT depends on multiple factors, which can be organized into four major categories: comorbid factors, patient factors, demographic factors and technical factors [Lee et al. 2003]. These four ‘survival factors’ may also interact with each other and cause increased
w w .AB B Y Y.c o
m w
w .AB B Y Y.c o
mortality. Although patients’ factors and demographic factors cannot be easily controlled or altered, other factors can be easily identifiable and correctable. The best strategy to improve the survival of patients on RRT is to identify high-risk patients and then allocate more resources to treat them.
Survival rates differ among countries and registries. International differences in the mortality of dialysis patients are probably related to differences in population demographics, renal disease, lifestyle and socioeconomic status. Therefore, it is extremely important to investigate survival of RRT patients in each country and to identify characteristic risk factors in order to improve outcomes.
The aim of the study
To estimate the survival of patients on chronic haemodialysis in Lithua-nia and to identify associated risk factors.
Objectives of the study
1. To estimate survival of patients who started chronic haemodialysis due to end-stage renal disease in Lithuania during the period of 1998–2005 and to investigate its dynamics.
2. To identify factors associated with the survival of patients on chronic haemodialysis.
3. To evaluate significance of combined influence of risk factors on mortality of patients on chronic haemodialysis.
4. To estimate benefits of early referral to a nephrologist.
5. To evaluate associations between referral pattern to a nephrologist and survival of patients on chronic haemodialysis.
SCIENTIFIC NOVELTY AND PRACTICAL
SIGNIFICANCE OF THE STUDY
Despite many technical advances in the medical care and in the delivery of dialysis over the past years, mortality and morbidity of dialysis patients remains persistently high and their quality of life is rather poor. It is known that survival of ESRD patients is significantly poorer when compared to patients with other major illnesses such as prostate and colon cancer. Cardiovascular disease mortality rates among all ESRD patients are
appro-w w .AB B Y Y.c o
m w
w .AB B Y Y.c o
ximately 10 to 20 times those in the general population. In order to impro-ve survival of patients on RRT, scientists look for methods and strategies to identify risk factors and to modify them.
In our study for the first time in Lithuania, survival of patients on chronic HD has been estimated. It allowed comparing the survival of HD patients in Lithuania with survival of such patients in other countries. It was shown that survival of HD patients in Lithuania is comparable with survival of dialysis patients in Europe and even better than survival of HD patients in the United States. The main finding of our study was decreasing one-year and early (within 3 months from the start of HD) mortality during the period of 1998–2005.
For the first time in Lithuania, risk factors associated with survival of patients on chronic HD have been investigated. From demographic factors, only age at the start of HD was associated with survival. The study re-vea-led that survival among HD patients was associated with underlying renal disease: it was worse in myeloma kidney, rapidly progressive glomerulo-nephritis, kidney amyloidosis, systemic diseases, diabetic nephropathy, better in hypertensive nephropathy, chronic pyelonephritis and interstitial nephritis and the best in chronic glomerulonephritis and polycystic kidney disease.
For the first time in Lithuania, relationships between dialysis dose and adequacy, and patients’ outcomes have been studied. From the beginning of the dialysis era, the issue of optimal dialysis dose and frequency has been a central topic in the delivery of dialysis treatment. Until now, the optimal level of haemodialysis and the best measure of haemodialysis adequacy have been therefore undefined. Our results suggested that higher dialysis dose was associated with better survival. A significant survival benefit was seen especially in women.
Another hot issue in nephrological community is anaemia management and optimal haemoglobin (Hb) level. For the first time in Lithuania, associations between anaemia and survival of patients on chronic HD have been investigated. The study results revealed that anaemia management in Lithuania is suboptimal. Hb concentration was an independent risk factor for increased HD patients’ mortality. The Hb level of <100 g/L was asso-ciated with a 2.5-fold increased mortality risk as compared with higher Hb level.
The late referral of patients with chronic renal failure may adversely affect outcomes of dialysis patients, theoretically in part due to failure to optimally manage the complications associated with renal failure (eg,
anae-w w .AB B Y Y.c o
m w
w .AB B Y Y.c o
mia, bone disease, dyslipidaemia). Compared to those referred late, early referral may be associated with the following potential benefits: informed selection of dialysis modality, timely placement of appropriate dialysis access, non-emergent initiation of dialysis, lower morbidity and improved rehabilitation, less frequent and shorter hospital stays, lower cost, improved survival and preemptive transplant. Despite all efforts to alert the medical community about its multiple detrimental consequences, late nephrological referral of renal patients still remains a frequent problem in all countries. Recent studies show that up to 40% of patients suffering from chronic renal insufficiency begin renal replacement therapy less than 6 months after being referred to a renal unit, without having benefited from early nephrological care in the predialysis period.
We analysed the quality of predialysis nephrological care in one tertiary HD centre during the period of 1998–2005. Our results revealed that late referral to a nephrologist, defined less than 4 months until HD initiation, was documented in 55.2% of cases. Patients, referred late, were in worse clinical condition: with more prominent anaemia, malnutrition, impaired inflammatory status; more than 77% of them were not prepared for HD treatment, because they did not have a matured arteriovenous fistula at the start of HD. Survival of late referrals was significantly poorer comparing with early referrals. It suggests the need of developing a targeted programme of medical and teaching intervention to meet the specific needs of incident haemodialysis patients in order to reduce morbidity and mortality.
MATERIALS AND METHODS
Study populationAll patients who started chronic HD due to ESRD in Lithuania between 1 January, 1998, and 31 December, 2005, were enrolled in our study.
Because there is no official renal registry in Lithuania, in December of each year, all HD centres of Lithuania were visited by workers of the Department of Nephrology of the Hospital of Kaunas University of Medi-cine, and data on all HD patients were collected, using special paper ques-tionnaires. Using data, collected at annual visits to HD centres, demo-graphic data, cause of ESRD, date of HD start and how it was started, the duration of HD (hours per week), HD quality (single-pool Kt/V), Hb level and outcome were recorded for every patient in a special form.
Additional-w w .AB B Y Y.c o
m w
w .AB B Y Y.c o
ly, we collected data on some parameters at the start of HD (haemoglobin, C-reactive protein, serum albumin, creatinine, calcium, phosphate) and referral pattern to a nephrologist for patients who started HD in the HD Centre of the Hospital of Kaunas University of Medicine. Early referral was defined as a referral of the patient to a nephrologist at least 4 months prior to the first dialysis. In late referral group, we selected the urgent HD subgroup, when consultation of nephrologist was on the same day as the start of HD.
In order to compare results, all the patients were divided into several groups:
• Age groups, according to age at the start of HD:
o 0–19 years old, o 20–44 years old, o 45–64 years old, o 65–74 years old, o ≥ 75 years old;
• Primary renal disease groups, according to the primary cause of
ESRD:
o chronic glomerulonephritis, o diabetic nephropathy,
o hypertensive and/or ischaemic nephropathy, o other causes;
• First vascular access groups, according to vascular access used for
the first HD procedure:
o started HD through an arteriovenous fistula, o started HD through a central venous catheter. Statistical analysis
Some values are presented as mean±SD and others as a total number (percentage) or numbers per million of population (p.m.p.). The statistical analysis was performed using the SPSS programme (version 15.0, SPSS Inc. Chicago, IL, USA). Distribution of data for normality was tested using the Kolmogorov-Smirnov test, Lilliefors modification. Differences between groups of normally distributed data were tested using the Student’s t test for continuous variables, chi-square test for discrete variables, ANOVA test for more than two groups. Differences between groups of skewed data were compared using nonparametric methods: the Mann-Whitney U test for two groups and the Kruskal-Wallis H test for more than two groups. The Spearman’s rank correlation was employed to assess correlations
w w .AB B Y Y.c o
m w
w .AB B Y Y.c o
between parameters. For some laboratory parameters, ROC curves were used to assess the prognostic value and to compare their predictive value.
Analysing outcomes, we estimated mortality and survival rates.
Crude first-year mortality was calculated by dividing the number of patients who died during the first 12 months from the start of HD by the number of patients at risk during the same period. Early mortality rate was calculated by dividing the number of patients who died during the first 3 months from the initiation of HD by the number of patients at risk during the same period. Because not all of the patients completed a full year of dialysis therapy, death rate was computed on basis of follow-up time. As it is done by other renal registries, the mortality rate was expressed as the number of deaths per 1000 patient-years on renal replacement therapy. It was calculated by dividing the number of deaths by the total time in years that the patients were treated by HD, and multiplying by 1000. Because changes in age distribution of patients starting HD appeared during the study period, in order to compare mortality in different our study periods, we used standardized mortality ratio (SMR) defined as the observed mor-tality for a certain age group in a certain year divided by the expected mortality for the same age group and year.
The cumulative survival rate was estimated using the Kaplan-Meier method. The event of interest was death. Patients were censored at the time of transplantation or transfer to PD, loss to follow-up and at the end of the study. Survival comparisons were made using the log-rank or Breslow tests. Univariate Cox proportional hazards analysis was used to select variables significantly associated with the risk of death; then these variables were included in multivariate Cox proportional hazards models. Results considered significant at P<0.05.
RESULTS
The total number of investigated patients who started chronic HD due to ESRD in Lithuania during the period of 1998–2005 was 2 428. Male-to-female ratio was 1.07:1.0. Their mean age at the start of HD was 56.20±16.11 years. The causes of renal failure were the following: chronic glomerulonephritis, 22.5%; chronic interstitial nephritis or pyelonephritis, 23.8%; renal polycystosis, 7.2%; diabetic nephropathy, 21.2%; hypertensi-ve or ischaemic nephropathy, 11.7%; systemic diseases, 0.9%; amyloido-sis, 2.6%; myeloma kidney, 1.9%; others, 6.4%.
w w .AB B Y Y.c o
m w
w .AB B Y Y.c o
The total follow-up period was 56 059.12 months; the mean duration of follow-up for the entire cohort was 23.15±21.48 months.
The incidence rate of HD increased from 71.6 p.m.p. in 1998 to 102.8 p.m.p. in 2005 (Figure 1).
Figure 1. Incidence of HD in Lithuania during the period of 1998–2005.
During the study period, the mean age of the incident HD patients at the start of HD increased (Table 1). The percentage of patients starting HD at the age of 65–74 years increased from 19.52% in 1998 to 25.86% in 2005 and at the age of ≥ 75 years, from 1.59% in 1998 to 22.13% in 2005.
Table 1. Mean age of all patients and percentage of patients older than 65
years at the start of HD in Lithuania during 1998–2005 Start of
HD
Mean age at the start of HD (years) Percentage of patients aged 65–74 years Percentage of patients aged ≥ 75 years 1998 51.9±14.58 19.52 1.59 1999 52.2±16.03 20.14 3.82 2000 53.9±15.88 22.47 6.74 2001 55.9±16.17 30.21 5.90 2002 56.1±15.30 25.00 8.57 2003 57.8±16.07 25.63 13.80 2004 59.4±14.97 29.08 12.17 2005 60.1±17.38 25.86 22.13 w w .AB B Y Y.c o m w w .AB B Y Y.c o m
The epidemiology of dialysed patients has changed remarkably during the study period (Figure 2).
Figure 2. Distribution of incident HD patients according to the primary
cause of ESRD in Lithuania during 1998–2005
As it is shown in Figure 2, the rate of chronic glomerulonephritis de-creased from 29.8% in 1998 to 15.5% in 2005. There was an increase in the prevalence of diabetic nephropathy as primary kidney disease from 18.1% in 1998 to 23.9% in 2005. The prevalence of hypertensive nephro-sclerosis and/or ischaemic nephropathy increased even more – from 6.5% in 1998 to 18.4% in 2005.
At the end of the study, 1090 patients were still alive, 811 had died, 28 had transferred to PD, 260 had benefited from kidney transplantation and 235 had been lost to follow-up.
Total mortality rate for study population was 173.62 per 1000 patient-years. Comparing mortality during different study periods, we calculated a standardized mortality ratio, because significant changes appeared in age distribution of the patients. A decreasing mortality rate was observed during the study period. The results are presented in Table 2.
w w .AB B Y Y.c o
m w
w .AB B Y Y.c o
Table 2. Mortality of HD patients per 1000 patient-years at risk and
stan-dardized mortality ratio in Lithuania during 1998–2005 Start of HD,
year
Mortality rate per 1000 patient-years at risk Standardized mortality ratio 1998 195.04 1.0 1999 152.36 0.74 2000 153.55 0.68 2001 163.33 0.71 2002 139.15 0.58 2003 185.47 0.72 2004 222.88 0.90 2005 243.65 0.79
Analysing crude first-year mortality and early mortality (within 3 months from the initiation of HD), a significant decrease (P<0.001 and
P=0.002, respectively) was observed during the study period (Figure 3).
Figure 3. First-year and early mortality of HD patients
in Lithuania during 1998–2005
The main cause of death was cardiovascular diseases (32.1%); 13.4% of patients died from infectious complications; 10.5%, from sudden death; 3.4%, from cancer. In 25.4% of cases, the exact cause of death was not known or reported in medical documentation.
Using the Kaplan-Meier method, we estimated survival rate of patients on chronic HD in Lithuania during the period of 1998–2005. The 1-year survival rate was 79.6%; 2-year, 68.8%; 5-year, 49.4%.
w w .AB B Y Y.c o
m w
w .AB B Y Y.c o
The univariate Cox regression analysis revealed that each additional year of age at initiation of HD increased the risk of death by 2.8% (RR= 1.028, 95% CI 1.023–1.033, P<0.001). After adjusting for age, sex was not associated with survival.
In the univariate analysis, all main causes of ESRD were associated with mortality, but after adjusting for age, only patients with diabetic nephropa-thy had more than 2-fold increased risk of death (Table 3).
Table 3. Relative mortality risk of primary renal disease, adjusted for age
95% CI
Cause of ESRD RR P Lower
limit
Upper limit
Diabetic nephropathy 2.212 <0.001 1.779 2.75
Hypertensive or ischaemic nephropathy 1.209 0.172 0.921 1.587
Other 1.165 0.141 0.951 1.427
Age 1.030 <0.001 1.024 1.035
We estimated cumulative survival for hemodialysed diabetic and non-diabetic patients who started HD at different periods. Figure 4 presents a significant improvement in survival of all patients, but especially in diabetic patients on HD in Lithuania during the study period.
Figure 4. Comparison of cumulative 1-year, 2-year and 3-year
survival of patients with and without diabetes mellitus on chronic HD in Lithuania during the study period
w w .AB B Y Y.c o
m w
w .AB B Y Y.c o
Haemodialysis requires a stable vascular access to the bloodstream to permit dialysis to be performed. Recent clinical practice guidelines recommend the creation of an arteriovenous vascular access (i.e. native fistula or synthetic graft) before the start of chronic haemodialysis therapy to prevent the need for complication-prone dialysis catheters. Arteriove-nous fistula is the best access, associated with fewer complications, but some time is required for its proper maturation. Therefore, matured arterio-venous fistula at the initiation of chronic HD indicates planned HD start.
We collected data about an initial vascular access in Lithuania during the period of 2002–2005. From 1328 patients who started chronic HD during the mentioned period, information on vascular access in the records at the time of review was available for 901 patients (67.85%). At initiation of haemodialysis, 438 (48.61%) of 901 patients were using a catheter, and 463 (51.69%) were using an arteriovenous fistula. The patients did not differ significantly in terms of age, gender and primary kidney disease. During the period of 2002–2005, the proportion of patients starting HD through a central venous catheter increased from 44.51% in 2002 to 54.2% in 2005 (P=0.018) (Figure 5).
Figure 5. Proportion of patients starting chronic HD
through an arteriovenous fistula or a central venous catheter in Lithuania during 2002–2005 w w .AB B Y Y.c o m w w .AB B Y Y.c o m
Late referral to a nephrologic team, which has been reported in many countries, could be one possible explanation for the high proportion of catheter use. Predialysis care increases the likelihood of a permanent va-scular access at dialysis start. Our study supports this observation; we found that the proportion of new patients starting dialysis with a perma-nent access was higher when patients were seen for a longer predialysis period by a nephrologist. The mean proportion of catheter use in new pa-tients was 77.7% and 22.3% for papa-tients seen by a nephrologist < 4 months and ≥ 4 months, respectively, before starting dialysis.
In the Kaplan-Meier analysis, there was a statistically significant differ-rence between different primary vascular access groups, with the arteriove-nous fistula group having a greater survival (log-rank P<0.001).
In an unadjusted Cox proportional hazards regression model, catheter use was associated with a 2.2-fold increased relative risk of death (95% CI 1.63–2.99, P<0.001) as compared with the use of an arteriovenous fistula. Catheter use remained associated with a higher mortality risk after adjust-ment for age, gender and primary kidney disease (RR=2.19; 95% CI 1.62– 2.97, P<0.001).
The question as to the targets of dialysis dosing has been hot and controversial since the beginning of the long-term dialysis treatment era. Based upon observational studies and clinical randomized controlled trials, the optimal level of haemodialysis and the best measure of haemodialysis adequacy were therefore undefined. Observational evidence suggested a continuous benefit from increasing the delivered dialysis dose well above the minimal targets recommended by the international guidelines. The latter randomized controlled trials apparently concluded that there were no benefits to patients’ outcome from higher dialysis doses than those recom-mended by the present guidelines.
We decided to investigate dialysis dosing issues in Lithuania during the period of 1998–2005. From 2428 patients who started chronic HD during the mentioned period, information about HD procedure frequency and du-ration in the records at the time of review was available for 2063 patients (85%). Although the present guidelines recommend standard HD treatment at least four hours thrice weekly, only 58.5% of patients started HD in that schedule. More than one-third (36.2%) of patients were dialysed twice weekly, and 5.3% of patients started HD once weekly. The main reason for such dialysis prescription was insufficient HD network and limited access to HD treatment in the beginning of study period in Lithuania. Over the period of 1998–2005, the HD services significantly expanded in Lithuania.
w w .AB B Y Y.c o
m w
w .AB B Y Y.c o
Therefore, significant changes in HD prescription at the end of study pe-riod were observed: the proportion of patients who started HD thrice weekly increased from 45.9% in 1998 to 68.1% in 2005, twice weekly decreased from 42.4% in 1998 to 29.6% in 2005 and once weekly – from 10.7% in 1998 to 2.3% in 2005. There were no data about residual renal function at the start of HD; therefore, the reasons for lower HD dose prescription at the end of study were unknown.
Survival analysis revealed that patients dialysed ever fewer than three times per week or fewer than 10.5 hours per week survived shorter than patients receiving higher dialysis dose. Duration of HD session of ≤ 8 hours per week was an independent risk factor for mortality (Table 4).
Table 4. Effect of HD duration of ≤ 8 hours per week on relative mortality
risk, adjusted for age, sex and prevalence of diabetes
95% CI Factor Relative risk P Lower limit Upper limit
HD duration of ≤ 8 hours per week 1.983 <0.001 1.639 2.400
Age 1.025 <0.001 1.018 1.032
Sex 0.899 0.235 0.755 1.071
Diabetes mellitus 2.268 <0.001 1.861 2.765
We failed to prove survival advantage in patients who were dialysed ≥12 hours per week except those who started HD treatment in the period of 2002-2003 and women on dialysis for ≥30 months.
Higher dialysis dose depends on higher dialysis quality also. Traditionally, to evaluate adequacy of HD, estimation of Kt/V (urea) index is required. Kt/V is defined as the dialyzer clearance of urea (K, obtained from the manufacturer in mL/min, and periodically measured and verified by the dialysis team) multiplied by the duration of the dialysis treatment (t, in min) divided by the volume of distribution of urea in the body (V, in mL), which is approximately equal to the total body water. There is no universally accepted target value for the Kt/V. According to current guidelines, minimally adequate HD dose should be a Kt/V of 1.2.
During the study period, the mean Kt/V was 1.177±0.239. Higher Kt/V index was obtained in women and younger patients. It was depended on the duration of HD treatment: Kt/V was the smallest (1.16) in the first year
w w .AB B Y Y.c o
m w
w .AB B Y Y.c o
on HD and the greatest (1.37) in the seventh year of HD (P<0.001). Our data suggested that a higher Kt/V was beneficial (Table 5).
Table 5. Effect of Kt/V on relative mortality risk, adjusted for age and sex
95% CI
Factor Relative risk P
Lower limit Upper limit
Mean Kt/V < 1.0 1.0 Kt/V 1.0–1.19 0.622 <0.001 0.478 0.807 Kt/V 1.2–1.39 0.517 <0.001 0.387 0.690 Kt/V ≥ 1.4 0.713 0.037 0.518 0.980 Age 1.031 <0.001 1.023 1.039 Sex (female=1) 1.030 0.775 0.841 1.260
Table 5 presents the adjusted relative risk of death for patients’ groups with different Kt/V, selecting < 1.0 as reference Kt/V range. Even after adjustment for age and sex, a significant decrease in the probability of death was seen in all Kt/V categories above 1.0.
Another hot issue in nephrology is anaemia management. Anaemia is a common comorbidity associated with chronic kidney disease. Regardless of the aetiology, anaemia in chronic kidney disease results in fatigue, reduced exercise capacity, impaired cognitive and immune function, and reduced quality of life. Moreover, anaemia significantly contributes to disease burden by causing or exacerbating existing comorbidities.
We analysed severity of anaemia and its associations with mortality in patients on chronic HD in Lithuania in 1998–2005. Analysis revealed that the mean Hb value was 101.28±12.59 g/L; in males it was higher than in females (102.337±12.52 g/L vs 100.01±12.56 g/L, P<0.001) and did not differ comparing different age groups and primary renal disease groups.
The K/DOQI guidelines and the European Best Practice Guidelines have recommended a haemoglobin target of 110 to 120 g/L and >110 g/L, respectively. According to current national algorithm for the management of anaemia in Lithuania, from 2000, the target Hb level in patients on chronic HD is between 100 g/L and 105 g/L. In our study, only 20.2% of patients had such mean Hb concentration, 42.4% of patients had Hb level below the national Hb target, 19.6% of patients had Hb concentration in the range of 110–120 g/L, and in 5.7% of patients, the mean Hb level was >120 g/L. w w .AB B Y Y.c o m w w .AB B Y Y.c o m
Multivariate Cox proportional hazards analysis revealed that anaemia was an independent risk factor of death (RR=0.952, 95% CI 0.945–0.959,
P<0.001). Relative risk of mortality was 5% lower for every 1 g/L greater
Hb concentration when using the mean Hb level of each patient as continuous variable and adjusting for age, sex and primary kidney disease.
As shown in Table 6, the relationship of Hb level with mortality varied across different categories of Hb concentrations.
Table 6. Relative risk of death for haemoglobin categories
95% CI Mean Hb concentration
(g/L) Relative risk P Lower limit Upper limit
100–105 1.0 < 100 2.472 <0.001 1.923 3.177 106–109 1.076 0.687 0.754 1.534 110–120 1.058 0.731 0.767 1.459 121–130 1.031 0.915 0.593 1.791 > 130 2.356 0.063 0.953 5.822
Patients with haemoglobin level of 100 to 105 g/L were selected as the reference group. The haemoglobin concentration below 100 g/L was asso-ciated with a 2.5-fold increased relative risk of death. Haemoglobin levels of > 106 g/L were not associated with a lower risk of death. For Hb con-centrations of 130 g/L or greater, a trend towards a higher mortality risk was observed (RR=2.356, 95% CI 0.953–5.822, P=0.063), but it did not reach statistical significance.
Hb concentration at the start of HD was not associated with survival of patients in our study (RR=0.997, 95% CI 0.986–1.008, P=0.58).
Another big problem in management of chronic kidney disease patients is referral pattern to a nephrologist. Patients with chronic renal failure are referred to nephrologists either early (usually for help in diagnostic and management issues) or late (usually considered late if referred shortly prior to the need for renal replacement therapy) in their clinical course. Besides
the surprising agreement on the beneficial and graded effect of early nephrological referral, late referral and unplanned start of dialysis is a relatively frequent finding worldwide.
We analysed duration and quality of predialysis nephrological care in one tertiary HD centre in Lithuania during the period of 1998–2005. Early referral was defined as referral of the patient to a nephrologist at least 4
w w .AB B Y Y.c o
m w
w .AB B Y Y.c o
months prior to the first dialysis. In late referral group, the urgent HD subgroup, when consultation of nephrologist was on the same day as the start of HD, was selected.
The main subjects’ characteristics are presented in Table 7.
Table 7. Characteristics of patients in different referral groups
Late referrals (n=182) Characteristic Early referrals ≥ 4 months (n=148) Referred <4 months prior to start of HD n = 97 Consulted on the same day HD started
n = 85
p
Sex, male:female 1:1 1:1 1.67:1 0.193
Mean age (years) 52.48±18.02 60.74±15.11 57.44±18.11 0.001
Cause of ESRD (%) 0.017 Glomerulonephritis 63.0 18.5 18.5 Hypertensive or ischaemic nephropathy 48.9 35.5 15.6 Diabetic nephropathy 36 33.3 30.7 Other causes 40 30.3 29.7
Primary vascular access (%) <0.001
Central venous catheter 22.3 63.9 100
Arteriovenous fistula 77.7 36.1 0
Our results revealed that late referral to a nephrologist, defined less than 4 months until HD initiation, was established in 55.2% of cases. Late referrals were older at the start of HD. It was not surprising that the best referral to a nephrologist was of patients, suffering from chronic glomeru-lonephritis, because traditionally nephrologists are responsible for such patients’ treatment. Worse referral was reported in cases of hypertensive or ischaemic nephropathy. More than 51% of them were referred late. The worst referral was among patients with diabetes mellitus: more than 60% of them were referred late and more than 30% were seen by a nephrologist on the same day HD started. The majority of patients referred to a nephro-logist in a timely manner tended to have a functioning permanent access at the start of dialysis compared to only a small minority of late referrals.
Patients referred late to a nephrologist invariably presented with bioche-mical indices of severe uraemia and an imminent need for dialysis compa-red to patients refercompa-red early; patients refercompa-red late also had a significantly
w w .AB B Y Y.c o
m w
w .AB B Y Y.c o
more severe anaemia, hypocalcaemia, hypoalbuminaemia and impaired inflammatory status (Table 8).
Table 8. Laboratory parameters of early and late referrals at the start of HD
Parameter Early referrals
(n=148) Late referrals (n=182) P Haemoglobin (g/L) 88.46±17.58 82.35±17.26 0.02 C-reactive protein (mg/L) 26.17±43.11 53.18±65.17 0.01 Albumin (g/L) 34.48±5.91 32.6±7.26 0.025 Creatinine (mmol/L) 747.39±243.47 883.23±388.57 <0.001 Calcium (mmol/L) 2.12±0.37 2.0±0.29 0.004 Phosphorus (mmol/L) 1.82±0.56 1.81±0.55 0.915 CaxP product (mmol2/L2) 3.74±1.05 3.62±1.11 0.379
Survival analysis showed a significant difference between the two referral groups: 1-year survival rates were 85.9% in the early referral and 66.7% in the late referral group, 2-year survival rates were 76.8% in the early referral and 55.6% in the late referral group, and 5-year survival rates were 61.2% in the early referral and 41.8% in the late referral group (log-rank P<0.001). In a Cox hazards regression model, late referral was associated with a greater risk of death (RR=1.908, 95% CI 1.298–2.805,
P=0.001).
Not only referral pattern was significantly associated with outcomes of patients on chronic HD. Some of laboratory parameters at the start of HD had a prognostic value. Prognostic predictive values of the six laboratory parameters (C-reactive protein (CRP), serum albumin, serum creatinine, Hb concentration, and calcium and phosphorus levels) at the start of HD were compared using the area under the curve (AUC) determined by ROC curve analysis (Table 9).
w w .AB B Y Y.c o
m w
w .AB B Y Y.c o
Table 9. Prognostic value of laboratory parameters at the start of HD
using ROC curves
95% CI
Laboratory parameter AUC P
Lower limit Upper limit
CRP 0.668 <0.001 0.585 0.751 Phosphorus 0.495 0.905 0.403 0.586 Serum albumin 0.677 <0.001 0.601 0.752 Serum creatinine 0.616 0.006 0.535 0.696 Calcium 0.452 0.252 0.375 0.530 Haemoglobin 0.530 0.468 0.450 0.610
As shown in Table 9, the biggest area under the curve was observed for serum albumin. C-reactive protein and serum creatinine might be good markers for the prediction of outcomes also. On the other hand, in our study, Hb concentration, calcium and phosphorus levels at the start of HD were not useful laboratory measurements in mortality prediction.
Malnutrition is an important problem in patients treated with chronic haemodialysis. There is no single measurement that can be used to deter-mine the presence of malnutrition. Therefore, a panel of measurements is recommended, including a measure of body composition, a measure of dietary protein intake and at least one measure of serum protein status. To assess nutritional status at the initiation of HD, we selected two widely used laboratory measurements in clinical practice: serum albumin and creatinine.
All patients were divided into three groups according to albumin concentration: <30 g/L, 30–40 g/L and >40 g/L. The groups did not differ by mean age (P=0.321), sex (P=0.458) primary kidney disease (P=0.09), severity of anaemia (P=0.182) and calcium and phosphorus concentrations (P=0.309 and P=0.212, respectively). More malnourished patients were observed in the late referral group (P=0.021). Positive correlations were found between serum albumin and serum creatinine (r=0.16, P=0.009), calcium (r=0.162, P=0.017) and haemoglobin (r=0.172, P=0.006). A nega-tive correlation was found between serum albumin and C-reacnega-tive protein (r=–0.377, P<0.001).
Survival analysis revealed significant differences comparing patients with different serum albumin levels, with the worst survival in the patients with the albumin level of <30 g/L (Figure 6).
w w .AB B Y Y.c o
m w
w .AB B Y Y.c o
Figure 6. Cumulative survival of patients with different
albumin concentrations
Albumin concentration at the start of HD was an independent risk factor for death after adjustment for age, sex and primary kidney disease. Cox proportional hazards analysis revealed that with every 1 g/L – increase in albumin concentration, mortality was decreased by 8% (RR=0.92, 95% CI 0.894–0.952, P<0.001). We did not find significant associations between serum creatinine concentration and survival of the patients on chronic HD.
Although poor nutrition is a common cause of hypoalbuminaemia in dia-lysis patients, a number of chronic inflammatory conditions can also re-duce the serum albumin concentration. Inflammatory processes are com-mon in individuals with ESRD. This is due to many underlying factors, including an enhanced incidence of infections (most commonly dialysis-access related), the uremic milieu, elevated levels of proinflammatory cy-tokines, frequent presence of widespread arteriosclerosis and others. Usually ESRD-associated chronic inflammation is assessed by increased C-reactive protein levels. We analysed inflammatory status of patients starting chronic HD. All patients were divided into two groups according to CRP level at the start of HD: normal CRP level group (CRP ≤ 5 mg/L) and elevated CRP level group (CRP > 5 mg/L). Patients with elevated CRP were older (61.38±16.38 years versus 49.91±17.81 years, P<0.001), more anaemic (Hb concentration 88.8±18.05 g/L versus 92.57±18.67 g/L,
P=0.006), more malnourished (albumin concentration 32.00±6.62 g/L
versus 35.97±5.81 g/L, P<0.001) and more frequently referred late to a
w w .AB B Y Y.c o
m w
w .AB B Y Y.c o
nephrologist prior the start of HD (65.5% versus 35.6%, P<0.001), as compared with patients with normal CRP level.
In Cox regression analysis, CRP was an independent risk factor for death: with every 10 mg/L – increase in CRP concentration, all-cause mortality was increased by 6% (RR=1.006, 95% CI 1.003–1.009, P<0.001) and cardiovascular mortality was increased by 7% (RR=1.007, 95% CI 1.002– 1.012, P=0.003), after adjusting for age, sex and primary kidney disease.
Using the ROC curve, we selected cut-off values of CRP and categori-zed patients in 5 groups. As shown in Table 10, the relationship of CRP level with mortality varied across different categories of CRP concent-rations.
Table 10. Cox proportional hazards model for CRP categories adjusted
for age, sex and primary cause of ESRD
95% CI
Variable RR P
Lower limit Upper limit
CRP ≤ 5 mg/L 1.0 CRP 5.1–10 mg/L 1.450 0.464 0.536 3.921 CRP 10.1–50 mg/L 2.273 0.022 1.123 4.598 CRP 50.1–100 mg/L 2.398 0.025 1.118 5.146 CRP >100 mg/L 4.918 <0.001 2.210 10.945 Age 1.016 0.051 1.000 1.033 Sex (female = 1) 1.630 0.045 1.011 2.629 Glomerulonephritis 1.0 Hypertensive nephropathy 0.973 0.962 0.320 2.960 Diabetic nephropathy 2.871 0.032 1.097 7.514
Other causes of ESRD 1.694 0.244 0.698 4.108
Patients with CRP levels of ≤ 5 mg/L were selected as the reference group. The CRP concentrations higher than 10 mg/L were associated with an increased relative risk of death. The highest mortality risk was observed in patients with CRP level of > 100 mg/L. Increased CRP concentration especially was associated with early mortality (within 3 months of HD therapy). The CRP level of 50.1 to 100 mg/L had increased early mortality risk up to 11.44 (95% CI 1.387–94.301, P=0.024), while CRP concentra-tion above 100 mg/L had increased early mortality risk up to 19.86 (95% CI 2.403–164.094, P<0.001) comparing with a CRP concentration of ≤ 5 mg/L. w w .AB B Y Y.c o m w w .AB B Y Y.c o m
Abnormal mineral metabolism in patients with ESRD is associated with bone and cardiovascular disease. The serum concentration of calcium, pho-sphorus and parathyroid hormone (PTH) provides the most readily available indication of the state of mineral metabolism. We analysed mineral metabo-lism status of patients starting chronic HD in one tertiary HD centre in Lithuania within the period of 1998–2005. Data about calcium and phospho-rus concentrations at the start of HD were collected. Information about PTH level was not available. Normal calcium concentrations (according to current guidelines, 2.10–2.37 mmol/L) were found only in 34.5% of patients; 55.6% of patients were hypocalcaemic and the remaining patients had elevated calcium concentration. Normal phosphorrus concentrations (according to current guidelines, 1.13–1.78 mmol/L) were found only in 44.6% of patients; 44.7% of patients had elevated phosphorus concentration, and 7.7% of patients had decreased phosphorus concentration. CaxP product level at the start of HD was calculated. For majority of patients (76.9%), it was in normal range (< 4.4 mmol2/L2). None of the markers of mineral metabolism was associated with survival of patients on chronic HD in our study.
Investigation and correction of modifiable risk factors is very important in order to improve outcomes of patients. Each of risk factors may act alone or in concert with the others to affect outcomes. Mortality risk according to number of risk factors was investigated. At first, we selected 5 risk factors established in the total HD patients’ population:
• ESRD cause – diabetic nephropathy,
• start of HD through a central venous catheter, • Hb concentration < 100 g/L,
• duration of HD < 10.5 hours per week, • Kt/V < 1.0.
Cox proportional hazards model is presented in Table 11.
Table 11. Cox proportional hazards model for the number of risk factors
95% CI
Number of risk factors RR P
Lower limit Upper limit
0 1.0 1 1.863 0.090 0.907 3.823 2 3.270 0.001 1.623 6.589 3 3.959 0.000 1.893 8.278 4 9.066 0.000 3.901 21.072 5 22.239 0.004 2.767 178.751 w w .AB B Y Y.c o m w w .AB B Y Y.c o m
Patients without risk factors were selected as the reference group. For patients with one risk factor, mortality risk did not differ from the reference group. For patients with more than one risk factor, mortality risk increased significantly. For those with all five risk factors, an increase in mortality risk exceeded 22 times comparing with patients without risk factors.
The same scenario was observed analysing risk factors at the start of HD. We selected 3 laboratory measurements at the start of HD: Hb concentration of < 100 g/L, serum albumin of < 30 g/L and CRP of > 10 mg/L. In patients with all three laboratory abnormalities, the relative risk increased to 7.084. But if additional risk factors were added – diabetic nephropathy or unplanned HD initiation through a central venous catheter – mortality risk increased to 9.542 and 21.12, respectively. The main finding was the fact that an increase in the number of risk factors resulted in a higher mortality risk than expected from the addition of the solo effects. There is evidence that correction of multiple risk factors and achieving multiple clinical targets may be associated with superior survival outcomes versus that observed with attaining fewer clinical targets or only one.
CONCLUSIONS
1. The estimated 1-year survival rate of patients on chronic HD in Lithuania during the period of 1998–2005 was 79.6%; 2-year, 68.8%; 5-year, 49.4%; 7-year, 37.9%. The median survival was 58.90 months (95% CI 53.15–64.65 months). Despite changes in distribution of age and primary renal disease, a significant improvement in 1-year and 2-year survival in all patients, especially in diabetic patients, was obser-ved during the study period.
2. Associations between survival of patients on chronic HD and the following risk factors were found:
a. age: each additional year of age at initiation of HD increased the risk of death by 2.8%;
b. cause of ESRD: the lower survival rate was documented for patients with diabetic nephropathy, myeloma kidney, rapidly progressive glomerulonephritis, systemic diseases, amyloidosis and ischaemic nephropathy;
c. primary vascular access: central venous catheter use was
associa-w w .AB B Y Y.c o
m w
w .AB B Y Y.c o
ted with a 2.2-fold increased relative mortality risk compared with use of an arteriovenous fistula;
d. HD dose and Kt/V: patients dialysed ever fewer than three times per week or fewer than 10.5 hours per week and with Kt/V of <1.0 survived shorter than patients receiving higher dialysis doses;
e. anaemia: the haemoglobin concentration below 100 g/L was asso-ciated with a 2.5-fold increased relative risk of death;
f. malnutrition and chronic inflammation at the start of HD: serum albumin level of <30 g/L and elevated CRP level were associated with an increased mortality risk.
3. Patients on chronic HD were affected by multiple risk factors. An increase in the number of risk factors resulted in a higher mortality risk than expected from the addition of the solo effects.
4. Early referral to a nephrologist was of great practical significance. Early referrals were better prepared for HD treatment, with better-corrected complications of renal failure (anaemia, malnutrition, inflammatory status abnormalities of mineral metabolism).
5. Referral pattern to a nephrologist was associated with survival of patients on chronic HD. Survival of patients referred ≥4 months prior the start of HD was better comparing with patients referred <4 months. Late referral increased the risk especially of early mortality.
RECOMMENDATIONS
1. In order to improve database of patients on chronic HD: a. to ensure accurate registration of patients in HD centres;
b. to prepare unified methodology of registration for all HD centres; c. to ensure accurate registration of outcomes;
d. to dedicate responsible for registration persons in HD centres; e. to create a national service responsible for data collection,
storage, protection and processing (National RRT Registry); f. to ensure timely transmission of data to Registry;
g. to analyse collected data and regularly report them during meetings of nephrologists or in medical literature.
w w .AB B Y Y.c o
m w
w .AB B Y Y.c o
2. In order to improve survival of patients on chronic HD: a. to try reach higher HD dose and adequacy;
b. to introduce modern methods of HD increasing HD dose;
c. to improve management of anaemia especially in predialysis pa-tients;
d. to create a unified system for the registration of HD quality para-meters, regularly analyse obtained data and try to eliminate deter-mined defects.
3. In order to improve predialysis care:
a. to ensure timely referral to a nephrologist, when glomerular filtration rate is <30 mL/min;
b. to educate society about causes, clinical symptoms and outcomes of chronic kidney disease, encouraging to assess the state of kidney function especially for high-risk groups (diabetes, arterial hypertension, cardiovascular diseases, systemic diseases, etc.); c. to collaborate with general practitioners, family doctors,
cardiolo-gists, endocrinolocardiolo-gists, rheumatologists teaching them to recog-nize symptoms of chronic kidney disease, to assess renal function and in case of progression of renal insufficiency to refer timely to a nephrologist;
d. in predialysis patients to try to control multiple risk factors: anae-mia, arterial hypertension, mineral metabolism abnormalities, malnutrition, chronic inflammatory processes;
e. to inform patients about methods of renal replacement therapy, their merits and limits, to help them to choose the best method according to clinical status of patients and socioeconomic condi-tions;
f. to create the most suitable, according to condition of vessels, per-manent vascular access timely in order to mature it until initiation of HD.
4. To stimulate research investigations in Lithuania in the fields of HD quality, management of patients on chronic HD and risk factors for mortality; to originate risk stratification systems and to create management and prevention programmes of risk factors.
w w .AB B Y Y.c o
m w
w .AB B Y Y.c o
LIST OF THE AUTHOR’S PUBLICATIONS
1. Stankuvienė A, Bumblytė IA, Kuzminskis V, Žiginskienė E, Balčiu-vienė V. Hemodialize gydomų pacientų išgyvenimas Lietuvoje (1998– 2005 m. duomenimis). Medicina (Kaunas) 2007;43 (pr.1):96–102. 2. Stankuvienė A, Kuzminskis V, Labutienė V, Sribikienė B, Gražulis S.
Hemodialize gydomų ligonių išgyvenimui įtakos turintys veiksniai (Kauno medicinos universiteto klinikų Hemodializių centro 1994– 2004 m. duomenys). 2005;41(pr.1):80–86.
3. Stankuvienė A, Sribikienė B, Kanišauskaitė E. Ambulatorinės nefrolo-ginės pagalbos svarba hemodializių pradžiai. Medicina (Kaunas) 2003; 39(pr.1):150–155.
Other publications
1. Žiginskienė E, Kuzminskis V, Stankuvienė A, Santockienė L ir kt. Hemodializės paslaugų raida Lietuvoje (1996–2003). Medicina (Kau-nas) 2005;41(pr.1):31–37.
2. Žiginskienė E, Kuzminskis V, Kupčinskas L, Stankuvienė A. Virusi-nių hepatitų kontrolė Lietuvos hemodializės centruose 1997–2001 metais. Medicina (Kaunas) 2003;39(pr.1):143–149.
3. Vaičiūnas K, Jievaltas M, Kuzminskis V, Bumblytė IA, Dalinkevičie-nė E, StankuvieDalinkevičie-nė A. Kidney transplantation in Kaunas University of Medicine Hospital during the years 2000–2006. Lietuvos gydytojo žurnalas. Kaunas. 2008 (Konferencijų tezės); Nr. 1, p.56.
4. Vaičiūnas K, Jievaltas M, Kuzminskis V, Bumblytė IA, Dalinkevi-čienė E, Stankuvienė A. Kidney transplantation in Kaunas University of Medicine Hospital during the years 2000–2006//European Urology Meetings: Abstracts of the EAU 1st North Eastern European Meeting (NEEM): Tampere, Finland, 14-15 September 2007. Amsterdam: Elsevier. (Poster session 2. Surgical techniques). 2007; Vol.2, iss. 4, Sept. p.24.
5. Vaičiūnas K, Jievaltas M, Kuzminskis V, Bumblytė IA, Stankuvienė A, Kanišauskaitė E. First experience of kidney transplantation in Kaunas medical university hospital in the years 2000–2004 // 4th Baltic States Meeting of the European Association of Urology: (Riga, June 3-4, 2005): Programme book of abstracts/European Association of Urology. Riga, 2005. (Moderated poster session II) p.109–110, no. 11. w w .AB B Y Y.c o m w w .AB B Y Y.c o m
SANTRAUKA
Darbo tikslas:Nustatyti pacientų, sergančių galutiniu inkstų nepakankamumu ir gydomų hemodializėmis, išgyvenimą bei su juo susijusius veiksnius.
Pagrindiniai uždaviniai:
1. Nustatyti pacientų, pradėtų gydyti hemodializėmis dėl galutinio inkstų nepakankamumo nuo 1998.01.01 iki 2005.12.31, išgyvenimą ir įvertinti jo dinamiką.
2. Nustatyti veiksnius, susijusius su hemodializėmis gydomų pacientų išgyvenimu.
3. Įvertinti kombinuoto rizikos veiksnių derinio poveikio reikšmę he-modializėmis gydomų pacientų mirtingumui.
4. Įvertinti ankstyvo pacientų nukreipimo nefrologui reikšmę.
5. Nustatyti ikidializinės nefrologo priežiūros trukmės sąsajas su he-modializėmis gydomų pacientų išgyvenimu.
Išvados:
1. Pacientų, pradėtų gydyti hemodialize 1998.01.01 – 2005.12.31 dėl galutinio inkstų nepakankamumo Lietuvoje, vienerių metų išgyveni-mas buvo 79,6 proc., dvejų – 68,8 proc., penkerių – 49,4 proc., septy-nerių – 37,9 proc., gyvenimo trukmės mediana – 58,90 mėn. Nors kas-met tarp pradedančiųjų gydymą hemodializėmis daugėjo vyresnio amžiaus pacientų bei didėjo sergančiųjų diabetine, hipertenzine ar išemine nefropatija dažnis, vienerių ir dvejų m. išgyvenimas nuo gydymo hemodializėmis pradžios dinamikoje pagerėjo.
2. Nustatytos hemodializėmis gydomų pacientų išgyvenimo sąsajos su šiais veiksniais:
• amžiumi, pradedant gydymą hemodializėmis: kiekvieni metai
di-dino mirties riziką 2,8 proc.;
• pagrindine liga, sukėlusia galutinį inkstų nepakankamumą:
trum-piau išgyveno sergantieji diabetine nefropatija, mielomine nefro-patija, greit progresuojančiu glomerulonefritu, sisteminėmis jun-giamojo audinio ligomis, inkstų amiloidoze, išemine nefropatija;
w w .AB B Y Y.c o
m w
w .AB B Y Y.c o
• pradine kraujagysline jungtimi, reikalinga hemodializės
proce-dūrai atlikti: pradėjusiųjų gydymą hemodializėmis pro centrinės venos kateterį mirtingumo rizika buvo didesnė 2,2 karto negu pradėjusiųjų pro arterioveninę fistulę;
• savaitine hemodializių doze ir hemodializės procedūros efekty-vumo žymeniu Kt/V: trumpiau išgyveno tie pacientai, kurie
buvo dializuoti rečiau negu 3 kartus per sav. bet kuriuo gydymo hemodializėmis periodu, kurių vidutinė savaitinė hemodializių trukmė buvo mažesnė negu 10,5 val., o vidutinis Kt/V – mažes-nis negu 1,0.
• mažakraujyste: vidutinė hemoglobino koncentracija kraujyje
mažesnė negu 100 g/l didino mirtingumo riziką beveik 2,5 karto;
• mitybos būkle ir uždegimine organizmo reakcija gydymo
hemo-dializėmis pradžioje: trumpiau išgyveno tie pacientai, kuriems
pradedant gydymą hemodializėmis buvo nustatyta ryški hipoal-buminemija <30 g/l ir padidėjęs C reaktyvaus baltymo kiekis. 3. Hemodializėmis gydomus pacientus veikė ne pavieniai rizikos
veiks-niai, bet jų visuma. Rizikos veiksnių derinio kombinuotas poveikis mirtingumui buvo didesnis negu atskirų veiksnių santykinių rizikų suma.
4. Nefrologo ikidializinės priežiūros savalaikiškumas turėjo didelės reikšmės. Ankstyvosios nefrologo priežiūros grupėje pacientai buvo geriau paruošti gydymui HD, nes dauguma jų gydymo hemodia-lizėmis pradžioje jau turėjo veikiančią arterioveninę fistulę. Šiems pacientams buvo geriau koreguotos inkstų nepakankamumo kompli-kacijos (mažakraujystė, mitybos ir uždegiminės organizmo būklės pokyčiai, kalcio ir fosforo apykaitos sutrikimai).
Ankstyvas pacientų nukreipimas nefrologui iki gydymo hemodializėmis pradžios buvo susijęs su ilgesne šių pacientų išgyvenimo trukme. Vėlyvas nukreipimas nefrologui ypač didino ankstyvojo mirtingumo riziką.
Rekomendacijos:
1. Siekiant pagerinti HD gydomų pacientų apskaitą Lietuvoje, reikėtų: a. užtikrinti tikslią HD gydomų pacientų registraciją HD centruose; b. paruošti vieningą registracijos metodiką visiems HD centrams; c. kruopščiai registruoti HD gydomų pacientų išeitis ir jų tikslią
datą; w w .AB B Y Y.c o m w w .AB B Y Y.c o m
d. HD centruose paskirti atsakingus už pacientų registraciją asme-nis;
e. sukurti tarnybą (pvz., Pakaitinės inkstų terapijos Lietuvoje Re-gistrą), kuri rūpintųsi duomenų rinkimu, kaupimu, saugojimu bei apdorojimu;
f. užtikrinti savalaikį HD gydomų pacientų duomenų perdavimą Registrui;
g. reguliariai analizuoti surinktus duomenis ir skelbti juos nefro-logų renginiuose ir medicininėje literatūroje.
2. Siekiant pagerinti HD gydomų pacientų išeitis, reikėtų:
a. atkreipti dėmesį į HD procedūros trukmę bei savaitinį dažnį, motyvuojant pacientus 4 val. ir ilgesnės trukmės procedūrai, ne rečiau kaip 3 kartus per savaitę;
b. įdiegti modernius dializės metodus, kurie leistų padidinti dia-lizės „dozę“;
c. pagerinti anemijos kontrolę, ypač ikidializiniame periode;
d. sukurti vieningą HD kokybės parametrų registracijos sistemą, nuolat analizuoti gautus rezultatus ir stengtis pašalinti nusta-tytus trūkumus.
3. Siekiant pagerinti ikidializinę pacientų, sergančių inkstų neapkanka-mumu, priežiūrą, reikėtų:
a. laiku nukreipti nefrologo konsultacijai, kai GFG < 30 ml/min.; b. šviesti visuomenę apie lėtinės inkstų ligos priežastis, klinikinius
požymius, pasekmes, raginant pasitikrinti inkstų būklę ypač di-desnės rizikos grupėms (sergantiesiems cukriniu diabetu, pirmi-ne hipertenzija, širdies ir kraujagyslių ligomis, sisteminėmis jungiamojo audinio ligomis ir kt.);
c. bendradarbiauti su bendrosios praktikos ir šeimos gydytojais, kardiologais, endokrinologais, reumatologais, mokant juos at-pažinti lėtinės inkstų ligos išraiškas, ištirti inkstų funkciją ir lai-ku nukreipti nefrologui, progresuojant inkstų nepakankamumui; d. gydant ikidializinius pacientus, kompleksiškai koreguoti rizikos veiksnius: anemiją, arterinę hipertenziją, kalcio ir fosforo apy-kaitos sutrikimus, mitybos būklę, sanuoti infekcijos židinius ir t. t.;
e. informuoti pacientus apie pakaitinės inkstų terapijos būdus, jų privalumus ir trūkumus, padėti pasirinkti tinkamiausią pagal
w w .AB B Y Y.c o
m w
w .AB B Y Y.c o
esamą klinikinę būklę ir socioekonomines sąlygas;
f. laiku suformuoti pastovią kraujagyslinę jungtį, kad iki HD pra-džios ji spėtų „subręsti“, individualiai įvertinant kraujagyslių būklę ir parenkant tinkamiausią jungtį, atsižvelgiant į chirurgi-nės pagalbos prieinamumą.
4. Skatinti mokslinius tyrimus Lietuvoje, tiriančius HD gydomų pacien-tų gydymo kokybę, įvairius mirtingumo rizikos veiksnius, jų pagrin-du sukurti rizikos stratifikavimo sistemas bei rizikos veiksnių pre-vencijos ir korekcijos programas.
w w .AB B Y Y.c o
m w
w .AB B Y Y.c o
CURRICULUM VITAE
Name: Asta
Surname: Stankuvienė
Address: Department of Nephrology, Kaunas University of Medicine
Eivenių str. 2, LT-50009 Kaunas, Lithuania
Phone: +370 37 326336, +370 614 89940
Fax: +370 37 326189
E-mail: astankuvienes@gmail.com
Medical Education:
1988–1994 Studies at the Faculty of Medicine, Kaunas University of Medicine
1994–1995 Residency of general practice, Kaunas 2nd Clinical Hospital 1995–1998 Residency of internal diseases,
Kaunas University of Medicine Hospital 1998-2000 Residency of Nephrology,
Kaunas University of Medicine Hospital
Current position:
Since 2000 Nephrologist, Department of Nephrology, Hospital of Kaunas University of Medicine
Membership of professional societies:
Lithuanian Society of Nephrology, Dialysis and Transplantation (member of Transplantation Committee)
European Dialysis and Transplant Association (ERA-EDTA)
Knowledge of languages: Lithuanian, English, Russian
w w .AB B Y Y.c o
m w
w .AB B Y Y.c o
