Riga Stradins University

Aivars Pētersons

Monograph

HOW TO DISCOVER AND TREAT RENAL DISEASES:

to contribute systemic scientific approach in nephrology

with particular implication on introduction of peritoneal

dialysis (renal replacement therapy) in Latvia and to

expand the role of renal ultrasonoscopy in the

nephrologists' practice

Doctorate work for doctor degree of medical sciences in internal

diseases

/specialty - nephrology/

Riga, 2005

The Doctorate work has been performed in the Centre of

Nephrology of P. Stradiņš Clinical University hospital from 1996 to

1998 and continued till the year 2005 for works mentioned in the list

of publications.

Work manager: Prof. Aivars Lejnieks

Reviewers: Prof. Andrejs Kalvelis

Prof. Vytautas Kuzminskis, Kaunas,

Lietuva Prof. Valdis Pīrags

Introduction

The Doctorate work is based on the book of A. Petersons, E.

Veverbrants, I. Lazovskis "How to discover and treat renal diseases"

(580 pages, published on 1998, Riga, author's edition of A.

Petersons, impression 1800 copies). The book is made as a

monograph of A. Petersons with participation of both inspirers of the

work, teachers and nephrology experts - Prof llmars Lazovskis

(chapter on the history of nephrology; 3% of the total amount)

and Prof Egils Veverbrants (chapter "Acid/alkali balance"; 9% of the

total amount).

The basis of the Doctorate work, working with a monograph "How to

discover and treat renal diseases" has been performed in P.

Stradins Clinical University hospital, Center of Nephrology from

1996 till 1998 and continued till the year 2005 for works mentioned

in the list of publications.

The monograph has served as a mean both for introduction of

peritoneal dialysis in Latvia and more extended integration of renal

ultrasonoscopy in the nephrological practice. The amount of specific

nephrological knowledge defined in the monograph has influenced

the development of clinical practice based on scientifically justified

evidences, including more extended use of glomerulonephritis

morphological classification. In addition, the monograph has not lost

its importance when evaluated after some time.

Topicality of the work

Nephrology as a specialty is undergoing rapid and radical changes

over last 20 years. Among disciplines of internal medicine due to

development of modern technologies, probably only in cardiology

the same serious development and changes of the specialty content

may be observed. At baseline nephrology science (Hamburger,

1963) was engaged in research and treatment of renal diseases, but

nowadays 80% of the nephrologists's attention and time is devoted

to renal replacement therapy (RRT) (haemodialysis, peritoneal

dialysis, kidney transplantation) and associated problems that both

clinically and scientifically include all organ systems of the human

body. In the practical medicine in Latvia from vital organs at

sufficient amount for public only kidneys may be replaced (at small

amount also heart and stem cell transplantation is being performed).

As known, in other developed countries also liver, lung and

pancreas may be transplanted, but no technological replacement

methods for these organs are available. RRT is a life saving therapy

and its costs are very high.

Therefore scientifically justified choice of the treatment method,

control and development may not be overestimated.

After recovery of independence in the nephrology in Latvia a big

influence of soviet traditions has been observed. The clinical

nephrology has developed separately from hemodialysis and

kidney transplantation. Peritoneal dialysis for first patients was

started only on 1994 with large organizational problems. In the

resident program of nephrology established at Riga Stradins

university on the basis of P. Stradins hospital Nephrology centers it

was impossible to get all the necessary knowledge in Latvian,

particularly detailed description of renal replacement methods,

including peritoneal dialysis, morphological classification of

glomerulopathies etc. Therefore availability of up-to-date

scientifically grounded material was very important and actual for

the development of the field.

Figure 1. Principal sheme of peritoneal dialysis

(Inflow bag on the right side, then intraabdominal dwell, and

outflow (left), attaching system 4 times daily as a standart)

Peritoneal dialysis (PD) is one of 3 (also hemodialysis and kidney

transplantation) renal replacement therapy methods used when the

patient kidneys are loosing their function due to disease.

Using natural functions of peritoneum as a filter, with peritoneal

dialysis it is possible to qualitatively maintain life for patients up to

20 years. In the middle of 80-ies due to development of PD

technologies and reduction of the risk of major complications

(peritonitis) this method has been used wider and wider all over the

world. Proportion of PD among dialysis patients in different countries

varies widely (see table 1), but on average it constituents

approximately 20 to 40%. At most the frequency of PD is influenced

by the medical funding model and the level of prosperity of the state

(PD is cheaper by up to 30% than HD), religion, traditions, social

situation.

Table 1. Proportion of peritoneal dialysis among dialysis patients

(National registers - ANZDATA, UK Renal Registry, ADR, USRDS

2002)

The main advantages of PD in comparison to hemodialysis (HD) are

the following:

1) low price - in developed countries up to -30%,

2) maintains residual renal function for long time allowing better

control of fluid exchange,

3) gives an opportunity to live for people living far away from

nephrology centers,

4) provides more active life style in the aspect of work and traveling,

etc.

Disadvantages of PD in comparison to HD are the risk of abdominal

cavity infection, reduction of peritoneal function after 4 to 7 years,

lower intensity and dose limitations for bigger individuals. Results of

modern studies suggest that 3 renal replacement therapy methods

do not compete mutually, but collaborate in the interests of the

patient and where scientifically and medically motivated choice of

RRT is implemented; all three of them are used in a dynamic

complex. In addition, lege artis PD should be used as the first

method (Fenton S. et al, 1997). Later when reduction of peritoneal

function and/or residual renal function occurs, planned switch to

hemodialysis may be performed. It is established that advantages of

PD concerning the risk of mortality and morbidity in comparison to

HD becomes equal after 2 to 4 years of dialysis (Vonesh E, 1997;

Blake P, 1998). Possibilities of kidney transplantation may be used

by maximum both in PD and HD patients. After transplantation, if

necessary, patients mostly continue with hemodialysis or in the

absence of vascular access - with peritoneal dialysis.

Till 1994 in Latvia this third renal replacement therapy method was

not available. Peritoneal dialysis has been introduced in the

Nephrology centre of P. Stradins clinical university hospital from

1994, starting with 2 patients and meeting large organizational and

financial difficulties. There was also no complete information on the

scientific background of the method and possibilities of use in our

conditions. They were characterized by poor social guaranties for

inhabitants, questionable hygienic conditions, insufficient network of

the out-patient medical care, lack of nephrologists and complete lack

of information on peritoneal dialysis. When starting introduction of

peritoneal dialysis a necessity of wide study on the scientific

background of the method among other renal replacement therapy

methods, as well as on practice of different centers in adaptation of

the method for local conditions becomes actual.

Ultrasonoscopy (US) is a non-invasive, informative, harmless, rapid

and cheap image diagnostic method. With progression of US

technology it as the one available only for radiologists in 80-ies now

has been used also in other fields - particularly

in gynecology and cardiology. The informativeness of the US

method depends largely not only on the equipment quality, but

especiallyon its user-specialist competence in particular specialty.

Therefore large advantages has the nephrologists himself when

examining a nephrological problem with US. From 1986

nephrologists have started to use US in their everyday practice in

Kidney transplantation and Nephrology centers of P. Stradins

hospital. This practice is introduced, gives invaluable information and

operativeness, economic benefit and findings of additional

symptoms. It was very essential to collect this experience, analyze it,

offer for critical review of other colleagues as a methodological

mean, include US as an integral part in the amount of specific

nephrological knowledge. We considered that not less actual task is

to advance particular hypotheses for further studies (diagnostic

importance of renal pyramides in interstitial nephritis, the role of

parenchymal oedema in evaluation of diabetes, the role of cortical

hyperechogenicity in graduation of chronic renal disease etc.).

Till the middle of 90-ies in the nephrology practice clinical

classification of glomerulonephrites (GN) by Tareyev (Tapeeb EM,

1975) has been used. However in the USA and Western Europe

glomerulonephrites are classified mostly by their morphologic

picture or at the syndrome level - by the leading syndrome, also in

everyday practice. Although the morphologic picture of GN has been

outlined also in Latvian sources (Bruveris, Cernevskis, Lazovskis,

1990), however at the level of general classification with

corresponding treatment methods and clinical syndrome it has not

been used. Thus very actual is a scientifically grounded choice,

introduction and use in the nephrology practice of CN classification

by morphologic forms. In parallel to this process it was necessary to

activate and optimize morphologic examination methods (PAS,

immuno hystochemistry, electron microscopy), from which to a large

extent depends nephrological quality in the light of morphological

classification.

Particularly actual in the aspect of clinical nephrology is correct

detection of renal function, as well as detection of early renal

dysfunction signs - minimally reduced glomerular filtration rate

(GFR) and microalbuminuria. More and more studies indicate

that these both symptoms are serious, independent factors of high

cardiovascular risk (Ritz E. et al, 2004). If the prevalence of terminal

renal failure requiring huge and increasing funding is relatively small,

than cardiovascular diseases, the background of which probably is a

minimal undiagnosed renal dysfunction, is a much more larger

burden for society both in the aspect of survival, quality of life and

medical expenses. Therefore research of issues associated with

renal function and prescribing of treatment is invaluably actual

problem of modern internal diseases.

Targets of the job

1. To create a scientifically sound, contemporary, scientifically

referenced minimum knowledge supply necessary for any

nephrologist.

2. To analyze literature about optimal possibilities of PD usage

in Latvia and to record the first experience about problems of

implementation of this kidney replacement therapy method.

3. To implement and develop scientifically proven, common

principles of PD usage in Latvia.

4. To trace the role of kidney US in nephrology practise and to

highlight hypothesesis about US symptoms based on

observations.

5. To create a scientifically sound classification based on GN

clinical syndrome and morphological picture and to implement

it in Latvia through motivations and descriptions.

6. To provide detailed analyses and information about early

functional renal examinations (GFR, MAU), considering their

significant effect on cardiovascular risk in population.

Tasks of the job

1. To perform detailed analyses of literature about each target

question.

1. To select, complement with experience of our centre and

record conclusions in an easy to publish and understand way.

3. To create basis for further researches with references to

originals, as well as to promote a discussion about problems

of clinical nephrology basing on research studies.

4. To assess influence of the monograph on nephrological

clinical studies and development of clinical practise.

5. To turn attention to language and terminology questions in

the field considering the size of edition which includes all

aspects of nephrology.

Novelty of the job

1. For the first time in Latvia - selected, referenced in the text,

essential and sufficient data intended for contemporary

nephrologist have been included in one book.

2. For the first time in Latvia - a detailed review of scientific

basis and practical usage of peritoneal dialysis method

(kidney replacement therapy) has been created.

3. On the ground of basis worked out in monograph following

has happened in Latvia:

a. scientifically sound methodology has been created

for PD usage,

b. a stabile managerial structure of PD has been

created on national level,

c. a data base of dynamic observations of PD patients

has been created in the Nephrology centre of P.

Stradins Clinical Hospital.

4. Analyses, detailed descriptions and illustrations about usage

and implementation of ultrasonography method in nephrology

has for the first time been given in special literature of

nephrology.

5. The job conveys hypothesis about relation between separate

US symptoms and certain nephropathy, the meaning of which

have been proved in clinical practise.

6. Close correlation of clinical syndrome and morphological

picture has been used and implemented in classification of

glomerulonephritis for the first time in Latvia.

7. Basis for referenced data base in nephrology field in Latvian

has been created for the very first time.

Job structure and size

Monograph „How to discover and treat renal impairments" is written

in Latvian language. It includes 20 chapters, 530 pages, 60 tables,

200 pictures, 660 references to the literature in the text

Most of ultrasonography images have been fixed in the result of

clinical observations of the author.

Pictures illustrating essential data about morphology of

glomerulopathia have been obtained due to cooperation with

internationally well-known nephropathologists - Prof. Helmut Rennke

and Prof. Jan Weening, as well as from personal archive of Prof.

Egils Veverbrants.

Results and discussion

In the monograph „How to discover and treat kidney impairments" all

aspects of modern nephrology have been considered, including

clinical nephrology with arterial hypertension and renal

pathomorphology, problems of water-salt balance, problems of

alkaline-acid balance, kidney replacement therapy - either

hemodialysis and peritoneal dyalisis, and principles of renal

transplantation. All the themes are described in an analytical way

basing on most important cognitive sources in nephrology, original

research studies. Selection has been made basing on practical

experience of authors in the field. Attempts are made to give most of

the references straight in the text (referenced). It facilitates the

reader to use source materials, promotes scientific discussion,

creates basis for further elaboration of the data base. Similar

contemporary monograph is not yet available in Estonia, Lithuania

or Finland. It has been widely used not only in the references of

other trials, in scientific and public articles, but has served as

cognitive source of minimum necessary knowledge

in Latvian for residents of internal diseases and nephrology,

nephrologists, professionals who are trained in peritoneal dialysis

method, e.c.t.

Table 2. Dynamics of development of PD program in Latvia

(data of LNSR)

Successful development of state program of peritoneal dialysis

may be considered as one of benefits from publication of the

monograph. Program of peritoneal dialysis in Latvia was started

with 2 patients in the Nephrology Centre of P.Stradins Clinical

Hospital in 1994. Henceforward despite of all difficulties the number

of patients treated with PD is growing (see table 2). By the help of

our Nephrology Centre, PD method was initiated in Nephrology

centres of Children's Hospital, Gailezers Hospital, which currently

are acting as completely independent centres and also in

Nephrology Centres of Valmiera and Liepaja Hospitals. PD problem

investigation in the monography „How to discover and treat renal

impairments?" serves as study aid for safe and precise usage and

implementationofthe method in big Nephrologycentres. It has

helped many people for whom dialysis and consequential survival

was not possible before PD implementation. This mainly refers to

patients who live far from Nephrology centres, elderly people and

children, diabetics and persons with different special needs with

moving difficulties, et c.

Either in the monograph and after it's publishing it was practically

proved that PD method does not compete with other RRT methods,

but mutually reinforce each other. Good renal transplantation results

were observed in patients who had received PD. It has proved to be

beneficial as also first RRT in patients with maintained residual

function of kidneys. Patients, who have protractedly received

hemodyalisis (which is the main and most intensive method of

dialysis) may experience vascular problems and if transplantation is

impossible, only PD may be helpful. The above mentioned and

several other criteria, including financial aspects, form rational

proportion of peritoneal dialysis and hemodialysis in countries where

choice of a certain RRT method is not influenced by private financial

interests. PD is at optimum used in 20 - 30% of dialysis patients.

Due to scientific approach and education, which has been promoted

by this monograph, proportion of PD among the other dialysis

methods in Latvia comes close to optimum (see Table 3)

Detailed studies, selection and pictorial description of US symptoms

characteristic to renal diseases has been performed. Algorithms of

interpretation of similar US examination results depending on a

patient's clinical condition have been offered. It is suggested to

implement a 4 stage classification for cortical

Table 3. Penetrance of PD method in dialysis (data of LNSR)

echogenity US description (Hricak H, 1982). It's advantages have

been tested in long-term practical observations as well as through

analyses of cortical echogenity related available literature.

Looking retrospectively classification of Hricak has turned out to

be useful and has widely spread among nephrologists and

radiologists in Latvia.

Figure 2. - 5. Grading of renal cortical echogenicity

(Grade 0-3, Hricak)

A conception about usage of US in nephrology practise has been

risen and motivated. Such approach in 1998 was observed only in

some centres of Germany (Koeppen-Hagemann, 1992) and

France, but in other countries, especially in USA ultrasonoscopy

was under responsibility of radiologists, moreover radiologists

were only analyzing standard images obtained by technicians.

Recently (Neil, 2002) USA also starts developing gradually the

nephrological way of US examination which is particularly described

in our monograph.

Morphological classification of glomerulopathias has been used for

detailed analyses of pathogenesis and therapy possibilities of

separate diseases. It has for the first time been completely reviewed

and used as basic classification for glomerulonephritis. Associations

with clinical glomerulal syndomes - nephrotic and nephritic - have

been highlighted and motivated.

Figure 6. FSGS in light microscopy (PAS)

Figure 7. IgA nephropathy (immunperoxidase)

Pathologies with variable study results or contradictory opinions of

different authors have been handled through scientific discussion

and open polemics. It has been reflected in the job. For example,

1) status of minimal change glomerulonephritis (MCG) as

an independent disease or as part of focal segmental

glomerulosclerosis (FSGS),

2) debated hypothesis about similarity or direct pathogenetic

relation of IgA nephropathy to Henoch-Scheonlein purpura

(HSP).

3) Hemolytic uremic syndrome (HUS) and thrombotic

thrombocytopenic purpura are included in a wider

pathogenically sound group - thrombotic microangiopathy

(TMA),

4) Not so widely used, but very practical 3-type division of

rapidly progressive glomerulonephritis (RPGN) has been

used.

The significant role of AKI for almost all patients with increased

blood-pressure or chronic renal disease has been highlighted in the

job. After 1998 when the monograph was published the meaning of

this therapy has been proven in new controlled studies

Additional hypothesis raised in the job

1. US oedema symptoms of renal parenchyme (thickness > 15

mm; kidney length > 12 cm; and cortical hypoechogenity) in

patients with short medical history of Type 1 diabetes mellitus

can indicate to diabetic metabolic decompensation and

glomerular hyperfiltration.

2. Increased echogenity of medullar pyramids may indicate to

an acute intersticial nephritis and may help in differential

diagnosis between mostly intersticial or glomerular

impairment.

3. US of kidneys should be preferably performed by the

nephrologist him-/herself on everyday basis.

Conclusions

1. The extent of specific knowledge and scientific conclusions in

nephrology should include the minimum which is reviewed in

the monograph and basically complies with UEMS

recommendations.

2. Also in Latvia PD is an effective kidney replacement therapy

method which does not compete with other methods, but

successfully incorporates in the common therapy complex.

3. The inclusion of US in the range of routine examinations of

nephrologists, especially if it is performed by a specialist

him-/herself significantly improves quality of diagnostics and

rate of examinations.

4. Cortical echogenity of kidneys, signs of oedema and the type

of medullar pyramids in US are relatively specific symptoms

for certain renal diseases and for clinical condition of a renal

patient.

Practical recommendations

1. In everyday diagnostics of glomerulopathies morphological

classification approved by renal biopsy should be used.

2. Peritoneal dialysis in patients without contraindications should

be used as first or initial renal replacement therapy method,

incorporating the two other methods later on during.

3. Nephrological or „blind" implantation of peritoneal dialysis

catheter is effective, quick, safe in all cases, when surgical

implantation is not indicated.

4. In all cases when US equipment is available, it is

recommended that a nephrologist him-/herself should perform

this examination.

5. Indirect US renal biopsy method combined with automatic

single-use biopsy needles (e.g. COOK) is good to be used in

everyday conditions of a nephrology unit to minimize the risks

of obtaining a qualitative bioptate.

Publikāciju saraksts

1. A. Pētersons - nodaļa „Nieru slimības", 120 Ipp. grāmatā "Internās slimības" A. Lejnieka redakcijā. 2005., NMA, Rīga, (pieņemts publicēšanai).

2. A. Pētersons - nodaļa „Nefroloģiskās rīcības labas prakses vadlīnijas" 21 lpp., grāmatā „P. Stradiņa slimnīcas Interno slimību ārstēšanas prakse" V. Pīrāga redakcijā, 2005., ISSA (pieņemts publicēšanai).

3. A. Pētersons, I. Daņiļēviča, H. Čerņevskis. Akūtas nieru mazspējas īpatsvars pacientu ar samazinātu nieru funkciju vidū Rīgā. RSU Zinātniskie raksti, 2005., (pieņemts publicēšanai).

4. Michule L, Adamsone I, Krastina E, Mihailova V, Petersons A, SpudassA, Babarykin D. Impact of predialysis erythropoietin treatment on the left ventricular hypertrophy, hospitalization rate and mortality in end stage renal disease (ESRD) patients after initiation of dialysis: a pharmacoeconomic analysis. 3rd Baltic Atherosclerosis congress 2004, Riga, Abstract, 57.lpp.

5. Diabētiskās nefropātijas diagnostika, ārstēšana un pacientu aprūpes principi (vadlīnijas) - autoru grupa - H. Čerņevskis, A. Galviņš, A. Helds, S. Lejniece, A. Lejnieks, A. Pētersons, V. Pīrāgs, 2004.g., 30. lpp., Rīga.

6. I. Mihailova, A. Pētersons, I. Jaunalksne, V. Mihailova, V. Priedīte. Perifēro mononukleāro šūnu apoptozes un aktivācijas izpēte hroniskas nieru mazspējas slimniekiem ar peritoneālo dialīzi. RSU, Zinātniskie raksti, 2003.

7. Mihailova I, Petersons A, Jaunalksne I, Priedite V. Increased level of apoptotic CD95+(Fas) and activated CD25+(IL-2RI) peripheral mononuclear cell (PMC) in patients with ESRD treated with PD. Nephrology Dialysis Transplantation 2003 Jun; 18(Suppl. 4), 767.

8. Petersons A., Stifts A., Tretjakovs P., Martinsons A., Jurka A. Skin microhemodynamics in patients with micro and macroproteinuria. Nephrology Dialysis Transplantation 2002; 17 (suppl) 225-225.

9. Donaldson K, Rossi M, MacLeod A, Petersons A et al. Incidence, prevalence and outcome in chronic renal failure in Eastern Europe - the results of the NACE study. Nephrology Dialysis Transplantation 2002; 17 (suppl) 246-247.

10.Hroniskas nieru mazspējas slimnieku ārstēšana. Kvalitātes standarts (vadlīnijas) - autoru grupa A. Pētersona vadībā, 1999., 7 Ipp., Rīga.

11.Petersons A, Ritz E. Nephrology in the Baltic countries. Nephrology Dialysis Transplantation 1998; 13: 2779-2780.

12. A. Pētersons, E. Vēverbrants, I.Lazovskis „Kā atklāt un ārstēt nieru slimības", zinātniska monogrāfija, 520 Ipp., 1998., Rīga, autorizdevums.

13. A. Pētersons. Nefroloģija Latvijā ārstu kongresu starplaikā. Latvijas Ārsts 1997; 6: 368-369. lpp.

14. A. Pētersons, Dz. Krugale. Peritoneālā dialīze Latvijā. Latvijas Ārstu žurnāls 1997; 9: 66-67.lpp.

15.ПЕТЕРСOНС А.А., ЛАЗОВСКИС И.Р. РОЛЬ УЛЬТРА-СОНОГРАФИИ В ДИФФЕРЕНЦИАЛЬНОЙ ДИАГНОСТИКЕ ГЕМАТУРИЧЕСКОГО ГЛОМЕРУЛОНЕФРИТА — 4. PSRS Nefrologu kongresa materiāli, Novosibirska, 1989.

Darba aprobācija (uzstāšanās, referāti):

1. Mnogrāfija KĀ ATKLĀT UN ĀRSTĒT NIERU SLIMĪBAS: sistēmiskas zinātniskas pieejas veicinātāja nefroloģijā ar īpašu ietekmi peritoneālās dialīzes (nieru aizstājterapija) metodes ieviešanā Latvijā un nieru ultrasonoskopijas lomas padziļināšanā nefrologa praksē. - Iekšķīgo slimību katedras sēde 2005.g. rudenī

2. "Earlv Renal Dvsfunction: pathogenetic link to arterial hvpertension" 3rd Baltie Nordic Meeting on Hvpertension, Vilnius, October 21, 2005.

3. Modernās nefroloģijas attīstība Latvijā - 5. Pasaules latviešu ārstu kongress, Rīga, 2005.

4. „Minor renal dysfunction: how to diagnose and treat"- 7th Baltic Conference of Nephrology, 2004., Riga

5. „How to Develop Peritoneal Dialysis Programme" - 1st Baltic Peritoneal Dialysis Meeting, 2003, Pernava, Igaunija

6. "Specificity of Development of Nephrology in Latvia" - 6th Conference of Baltic Societies of Nephrology, 2002, Kaunas, Lietuva

7. "Importance of Dialysate Quality in Peritoneal Dialysis"- Gambro Baltijas valstu konference, 2002., Rīga"

8. Hypertension in Kidney Disease" - 2nd Baltic - NordicMeeting on Hypertension, 2001. g., Rīga.

9. „Nieru aizstājterapija Latvija: nepieciešamība un iespējas" - 4. Pasaules latviešu ārstu kongress, 2001., Rīga.

10. „Renal replacement therapy in Latvia: era of rapid evolution" - Rochester General Hospital, University of Rochester, 2001., ASV, Rocestra.

11. Organization and epidemiology of RRT in Latvia" - NACE Study group, Aberdeen University, 2000, Aberdīna, AK.

12. „Epidemiology of ESRD in Latvia" - 4th Baltic Seminar of Nephrology, ERA-EDTA un ISN organizets, 1998., Rīga

13. Par monogrāfiju - KĀ ATKLĀT UN ĀRSTĒT NIERU SLIMĪBAS -RSU Iekšķīgo slimību katedras sēde (vad. Prof. J. Anšeļēvičs) 1998.g. novembrī

14. Par monogrāfiju - KĀ ATKLĀT UN ĀRSTĒT NIERU SLIMĪBAS - Latvijas Nefrologu asociācijas sēde, 1998.g. novembrī.