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					Chronic kidney disease.

Position paper 2007

Mai Rosenberg 1, Ruth Kalda 1, Vytautas Kasiulevičius 2 , Aivars Petersons 3,
Margus Lember 1

1 University of Tartu, Estonia
2 University of Vilnius, Lithania
3 Stradins Medical Academy, Riga, Latvia



Table of contents:


Introduction

Chronic kidney disease (CKD) is a worldwide public health problem that is often
under-diagnosed and under-treated.

Definitions and classification

Chronic kidney disease represents a progressive, irreversible decline in glomerular
filtration rate (1). Most chronic nephropathies unfortunately lack a specific treatment
and progress relentlessly to end stage renal disease. Progressive renal function loss is
a common phenomenon in renal failure irrespectively of the underlying cause of the
kidney disease (2).

In recent years the concept of chronic kidney disease has gained more attention
instead of chronic renal failure which is used to describe the more advanced stages of
CKD. This is especially important for primary health care where the role of primary
care providers is very important in handling the early phases of CKD to prevent or
postpone chronic renal failure. In the current literature the terms CKD, renal
insufficiency and renal failure are sometimes used without precisely defining these
conditions.

Chronic renal failure indicates to chronically (at least 3 months' duration) reduced
kidney function (clearance, glomerular filtration rate [GFR]). Renal function declines
normally with age, and exact level of decline at a given age that should be considered
pathological is not known.The Kidney Disease Improving Global Outcomes (KDIGO)
statement considers GFR less than 60 mL/minute pathological at all ages. However,
many elderly people have values less than this (in the USA, about 7% of white people
without diabetes who are aged in their 60s and 15% of those aged in their 70s), and
the extent to which low kidney function in the range of 30–60 mL/minute/1.73 m2 is
pathological or progressive in all people is a subject of some controversy. Though
people with end stage renal disease, by definition, have chronic failure of their
kidneys (which may have resulted from an acute or a chronic process) they are
generally not included in the term chronic renal failure, which in most of the literature
    and in this chapter refers exclusively to those with low kidney function who are not
    treated with renal replacement therapy.

    Chronic kidney disease defined by the Kidney Disease Improving Global Outcomes
    (KDIGO) statement as either the presence of abnormalities in urine or imaging that
    may lead to progressive disease or creatinine clearance (or glomerular filtration rate)
    less than 60 mL/minute/1.73 m2 . Chronic kidney disease includes chronic renal
    failure, but also includes predictors of chronic renal failure in people with normal
    kidney function (e.g. proteinuria), and end stage renal disease.

    The National Kidney Foundation - Kidney Disease Outcomes Quality Initiative
    (NKF-K/DOQI) workgroup has defined CKD as the following (10) which have been
    accepted internationally with some clarifications (7,11):

           The presence of markers of kidney damage for 3 months, as defined by
    structural or functional abnormalities of the kidney with or without decreased
    glomerular filtration rate (GFR), that can lead to decreased GFR, manifest by either
    pathological abnormalities or other markers of kidney damage, including
    abnormalities in the composition of blood or urine, or abnormalities in imaging tests

            OR

           The presence of GFR <60 mL/min/1.73 m2 for 3 months, with or without
    other signs of kidney damage as described above.

    Based upon representative samples of the United States population (12), the studies
    have estimated the prevalence of CKD in the general population through
    measurement of markers of kidney damage, such as elevated serum creatinine
    concentration, decreased predicted GFR, and presence of albuminuria. The term
    ―albuminuria‖ should be substituted for terms ―microalbuminuria‖ and
    ―macroalbuminuria‖. Increased urinary albumin excretion of albumin is the earliest
    manifestation of CKD due to diabetes, other glomerular diseases and hypertensive
    nephrosclerosis. Albuminuria may also accompany tubulointerstitial diaseases,
    polycysistic kidney disease, and kidney disease in transplant recipients (11).
    According to the KD:IGO position statement (11) the use of the term ―disease‖ in
    CKD is consistent with: 1) the need for action to improve outcomes through
    prevention, detection, evaluation and treatment; 2) providing a message for public,
    physician and patient education programs; 3) common usage; and 4) its use in other
    conditions defined by findings and laboratory tests, such as hypertension, diabetes,
    and hyperlipidemia (11).

    Classification of CKD.
    CKD classified according to the severity, diagnosis, treatment and prognosis (11).
    Suffix ―T‖ is used for all transplant recipients, at any level of GFR and, ―D‖ for
    dialysis, for CKD stage 5 patients treated with dialysis. Clinical evaluation for CKD
    should include elucidation of the cause of disease. However, cause of the disease
    cannot be ascertained in all cases.

    Table
    Stage           Description        GFR (mL/min Related terms
                                 per 1.73 m2)
1               Kidney damage ≥ 90                Albuminuria
                with normal or                    Proteinuria
                ↑ GFR                             Hematuria
2               Kidney damage 60-89               Albuminuria         ―T‖ if kidney
                with mild ↓                       Proteinuria         transplant
                GFR                               Hematuria           recipient
3               Moderate     ↓ 30-59              Chronic renal
                GFR                               insufficiency
                                                  Early       renal
                                                  insufficiency
4               Severe ↓ GFR     15-29            Chronic renal
                                                  insufficiency
                                                  Late        renal
                                                  insufficiency
                                                  Pre-ESRD
5               Kidney failure   < 15             Renal failure       ―D‖ if dialysis
                                                  Uremia              (HD, PD)
                                                  End-stage renal
                                                  disease




References

    1. Anderson, Brenner
    2. Ots M, Pechter U, Tamm A: Characteristics of progressive renal disease. Clin
       Chim Acta 2000;2971-2:29-41.
    3. Moeller S, Gioberge S, Brown G: ESRD patients in 2001: global overview of
       patients, treatment modalities and development trends. Nephrol Dial
       Transplant 2002;1712:2071-2076.
    4. Jager KJ, van Dijk PC. Has the rise in the incidence of renal replacement
       therapy in developed countries come to an end? Nephrol Dial Transplant
       2007;22:678-680
    5. U.S. Renal Data System, USRDS 2006 Annual Data Report: Atlas of End-
       Stage Renal Disease in the United States, National Institutes of Health,
       National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda,
       MD, 2006. Am J Kidney Dis 2006; 47(Suppl 1):S1.
    6. Locatelli F, D'Amico M, Cernevskis H, Dainys B, Miglinas M, Luman M, Ots
       M, Ritz E: The epidemiology of end-stage renal disease in the Baltic
       countries: an evolving picture. Nephrol Dial Transplant 2001;167:1338-1342.
   7. Gregorio T Obrador, Brian JG Pereira. Epidemiology of chronic kidney
       disease and screening recommendations. UpToDate 2007; 15
   8. http://www.musili.fi/fin/munuaistautirekisteri/
   9. K. Kõlvald,…. Renal replacement therapy trends in Estonia. Transplant Int
       2007:
   10. K/DOQI clinical practice guidelines for chronic kidney disease: evaluation,
       classification, and stratification. Am J Kidney Dis 2002; 39:S1.),
   11. Levey, AS, Eckardt, KU, Tsukamoto, Y, et al. Definition and classification of
       chronic kidney disease: A position statement from Kidney Disease: Improving
       Global Outcomes (KDIGO). Kidney Int 2005; 67:2089.
   12. Baigent C, Burbury K, Wheeler D: Premature cardiovascular disease in
       chronic renal failure. Lancet 2000;3569224:147-152.
   13. Coresh, J, Astor, BC, Greene, T, et al. Prevalence of chronic kidney disease
       and decreased kidney function in the adult US population: Third National
       Health and Nutrition Examination survey. Am J Kidney Dis 2003; 41:1.
   14. Foley RN, Parfrey PS, Sarnak MJ: Clinical epidemiology of cardiovascular
       disease in chronic renal disease. Am J Kidney Dis 1998;325 Suppl 3:S112-
       119.
   15. Pereira, BJG. Optimization of pre-ESRD care: The key to improved dialysis
       outcomes. Kidney Int 2000; 57:351.
   16. Orth SR, Ritz E: The renal risks of smoking: an update. Curr Opin Nephrol
       Hypertens 2002;115:483-488.
   17. Ritz E, Orth SR: Nephropathy in patients with type 2 diabetes mellitus. N Engl
       J Med 1999;34115:1127-1133.
   18. Shlipak MG, Simon JA, Grady D, Lin F, Wenger NK, Furberg CD: Renal
       insufficiency and cardiovascular events in postmenopausal women with
       coronary heart disease. J Am Coll Cardiol 2001;383:705-711.
   19. Amann K, Tornig J, Kugel B, Gross ML, Tyralla K, El-Shakmak A, Szabo A,
       Ritz E: Hyperphosphatemia aggravates cardiac fibrosis and microvascular
       disease in experimental uremia. Kidney Int 2003;634:1296-1301.
   20. Eknoyan G, Levey AS, Levin NW, Keane WF: The national epidemic of
       chronic kidney disease. What we know and what we can do. Postgrad Med
       2001;1103:23-29: quiz 28
   21. Meyer KB, Levey AS: Controlling the epidemic of cardiovascular disease in
       chronic renal disease: report from the National Kidney Foundation Task Force
       on cardiovascular disease. J Am Soc Nephrol 1998;912 Suppl:S31-42.
   22. Holley, JL, Nespor, SL. Nephrologist-directed primary health care in chronic
       dialysis patients. Am J Kidney Dis 1993; 21:628
   23. Schwartz, JS, Lewis, CE, Clancy, C, et al. Internists' practice in health
       promotion and disease prevention: A survey. Ann Intern Med 1991; 114:46.
   24. Zimmerman, DL, Selick, A, Singh, R, Mendelssohn, DC. Attitudes of
       Canadian nephrologists, family physicians and patients with kidney failure
       toward primary care delivery for chronic dialysis patients. Nephrol Dial
       Transplant 2003; 18:305.)
   25. Jean L Holley. The nephrologist as primary care physician in patients with
       end-stage renal disease. UpToDate 2007; 15
   26. Inglismaal tehtud töö NDT, 2007

www.clinicalevidence.org
Epidemiology and causes of CKD

Very few of the causes of chronic renal failure are completely curable. It is often not
necessary to do extensive tests to find a cause, however, for determining the stage and
specific characteristics of the underlying disese follow-up of patients and thorough
diagnostic work-up is needed. The three major groups of diseases leading to chronic
kidney failure are diabetes, hypertension and renal diseases (mostly
glomerulonephritides, tubulointerstitial nephritides and hereditary nephropathies, in
particular autosomal dominant polycystic kidney disease ADPKD). In different
countries the proportions of these diseases as a cause of renal failure are different.
However, in the western world the share of diabetes is steadily increasing.

Out of the advanced or end-stage renal failure (Siegenthaler) in the UK diabetic
nephropathy constitues 19%, hypertension 15%, chronic glomerulonephrits 10%,
chronic tubulointerstitial nephritis 6%, ADPKD 6%.
In the US diabetic nephropathy is the cause of chronic renal failuer even in 45%,
hypertension in 27%, chronic glomerulonephritis in 11% of cases while chronic
tubulointerstitial nephritis only in 3% and ADPKD in 2%. In Japan chronic
glomerulonephritis is the main reason (47%), diabetic nephropathy 30%, hypertension
10%, chronic tubulointerstitial nephritis 2% and ADPKD in 2% of cases.


Diabetes is one of the commonest causes of kidney failure in many countries (3,4,5).
However, in Baltic countries diabetes epidemic has not been yet seen and patients
with chronic glomerulonephritis usually form the main contingent of the end-stage
renal disease (ESRD) population (6). In many countries there is a rising incidence and
prevalence of kidney failure (3,4,5,6). Although the exact reasons for the growth of
the ESRD patients are unknown, it is postulated that changes in the demographics of
the population, differences in disease burden among racial groups and under-
recognition of earlier stages of CKD and of risk factors for CKD, may partially
explain this growth (7). However, recent trends show that the rate of increase of new
cases of both diabetic and all-cause ESRD has progressively flattened in many
countries (4,8) but this tendency is not universal and not seen in other populations (9).
However, it is currently impossible to predict the long-term trend in the incidence
rates of RRT in Europe. Therefore, secondary prevention should be organized as
effective as possible at the population level.

The prevalence and incidence of kidney failure treated by dialysis and transplantation
in the United States have increased from 1988 to 2004. Whether there have been
changes in the prevalence of earlier stages of chronic kidney disease (CKD) during
this period is uncertain. The prevalence of CKD in the United States in 1999-2004 is
higher than it was in 1988-1994. This increase is partly explained by the increasing
prevalence of diabetes and hypertension and raises concerns about future increased
incidence of kidney failure and other complications of CKD. / Coresh J, Selvin E,
Stevens LA, Manzi J, Kusek JW, Eggers P, Van Lente F, Levey AS. Prevalence of
chronic kidney disease in the United States. JAMA. 2007;298:2038-47/
The prevalence of CKD in the US adult population was 11% (19.2 million). By stage,
an estimated 5.9 million individuals (3.3%) had stage 1 (persistent albuminuria with a
normal GFR), 5.3 million (3.0%) had stage 2 (persistent albuminuria with a GFR of
60 to 89 mL/min/1.73 m(2)), 7.6 million (4.3%) had stage 3 (GFR, 30 to 59
mL/min/1.73 m(2)), 400,000 individuals (0.2%) had stage 4 (GFR, 15 to 29
mL/min/1.73 m(2)), and 300,000 individuals (0.2%) had stage 5, or kidney failure.
Aside from hypertension and diabetes, age is a key predictor of CKD, and 11% of
individuals older than 65 years without hypertension or diabetes had stage 3 or worse
CKD. / Coresh J, Astor BC, Greene T, Eknoyan G, Levey AS. Prevalence of chronic
kidney disease and decreased kidney function in the adult US population: Third
National Health and Nutrition Examination Survey. Am J Kidney Dis. 2003;41:1-12./




References:
Siegenthaler W. Differential diagnosis in internal medicine. Thieme. Stuttgart New
York 2007
   1. Anderson, Brenner
   2. Ots M, Pechter U, Tamm A: Characteristics of progressive renal disease. Clin
       Chim Acta 2000;2971-2:29-41.
   3. Moeller S, Gioberge S, Brown G: ESRD patients in 2001: global overview of
       patients, treatment modalities and development trends. Nephrol Dial
       Transplant 2002;1712:2071-2076.
   4. Jager KJ, van Dijk PC. Has the rise in the incidence of renal replacement
       therapy in developed countries come to an end? Nephrol Dial Transplant
       2007;22:678-680
   5. U.S. Renal Data System, USRDS 2006 Annual Data Report: Atlas of End-
       Stage Renal Disease in the United States, National Institutes of Health,
       National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda,
       MD, 2006. Am J Kidney Dis 2006; 47(Suppl 1):S1.
   6. Locatelli F, D'Amico M, Cernevskis H, Dainys B, Miglinas M, Luman M, Ots
       M, Ritz E: The epidemiology of end-stage renal disease in the Baltic
       countries: an evolving picture. Nephrol Dial Transplant 2001;167:1338-1342.
   7. Gregorio T Obrador, Brian JG Pereira. Epidemiology of chronic kidney
       disease and screening recommendations. UpToDate 2007; 15
   8. http://www.musili.fi/fin/munuaistautirekisteri/
   9. K. Kõlvald,…. Renal replacement therapy trends in Estonia. Transplant Int
       2007:
   10. K/DOQI clinical practice guidelines for chronic kidney disease: evaluation,
       classification, and stratification. Am J Kidney Dis 2002; 39:S1.),
   11. Levey, AS, Eckardt, KU, Tsukamoto, Y, et al. Definition and classification of
       chronic kidney disease: A position statement from Kidney Disease: Improving
       Global Outcomes (KDIGO). Kidney Int 2005; 67:2089.
   12. Baigent C, Burbury K, Wheeler D: Premature cardiovascular disease in
       chronic renal failure. Lancet 2000;3569224:147-152.
   13. Coresh, J, Astor, BC, Greene, T, et al. Prevalence of chronic kidney disease
       and decreased kidney function in the adult US population: Third National
       Health and Nutrition Examination survey. Am J Kidney Dis 2003; 41:1.
   14. Foley RN, Parfrey PS, Sarnak MJ: Clinical epidemiology of cardiovascular
       disease in chronic renal disease. Am J Kidney Dis 1998;325 Suppl 3:S112-
       119.
   15. Pereira, BJG. Optimization of pre-ESRD care: The key to improved dialysis
       outcomes. Kidney Int 2000; 57:351.
   16. Orth SR, Ritz E: The renal risks of smoking: an update. Curr Opin Nephrol
       Hypertens 2002;115:483-488.
   17. Ritz E, Orth SR: Nephropathy in patients with type 2 diabetes mellitus. N Engl
       J Med 1999;34115:1127-1133.
   18. Shlipak MG, Simon JA, Grady D, Lin F, Wenger NK, Furberg CD: Renal
       insufficiency and cardiovascular events in postmenopausal women with
       coronary heart disease. J Am Coll Cardiol 2001;383:705-711.
   19. Amann K, Tornig J, Kugel B, Gross ML, Tyralla K, El-Shakmak A, Szabo A,
       Ritz E: Hyperphosphatemia aggravates cardiac fibrosis and microvascular
       disease in experimental uremia. Kidney Int 2003;634:1296-1301.
   20. Eknoyan G, Levey AS, Levin NW, Keane WF: The national epidemic of
       chronic kidney disease. What we know and what we can do. Postgrad Med
       2001;1103:23-29: quiz 28
   21. Meyer KB, Levey AS: Controlling the epidemic of cardiovascular disease in
       chronic renal disease: report from the National Kidney Foundation Task Force
       on cardiovascular disease. J Am Soc Nephrol 1998;912 Suppl:S31-42.
   22. Holley, JL, Nespor, SL. Nephrologist-directed primary health care in chronic
       dialysis patients. Am J Kidney Dis 1993; 21:628
   23. Schwartz, JS, Lewis, CE, Clancy, C, et al. Internists' practice in health
       promotion and disease prevention: A survey. Ann Intern Med 1991; 114:46.
   24. Zimmerman, DL, Selick, A, Singh, R, Mendelssohn, DC. Attitudes of
       Canadian nephrologists, family physicians and patients with kidney failure
       toward primary care delivery for chronic dialysis patients. Nephrol Dial
       Transplant 2003; 18:305.)
   25. Jean L Holley. The nephrologist as primary care physician in patients with
       end-stage renal disease. UpToDate 2007; 15
   26. Inglismaal tehtud töö NDT, 2007
   27.


Screening

Early treatment of chronic kidney disease and its complications may delay or prevent
the development of end-stage renal disease, therefore detection of chronic kidney
disease is believed to be a priority for primary care. (Snyder S, Pendergraph B 2005)
There are reports suggesting that chronic kidney disease often is not detected, even
when patients have access to primary care. (National Kidney Foundation. 2003;
McClellan WM et al 2003)

Which patients to screen? There is overwhelming consensus that screening for
chronic renal disease should include high-risk groups. These include patients who
have a family history of the disese, patients who have diabetes, hypertension,
recurrent urinary tract infections, urinary obstruction or a systemic illness that affects
the kidneys (National Kidney Foundation. 2002). Screening for asymptomatic persons
beyond the above-mentioned patient groups has not found justification. The only
exception are pregnant women: screening for bacteriuria is justified and its effect
proven as the treatment of asymptomatic bacteriuria has been found to be effective in
benefit of newborns /US Task Force..../

How to screen? The most widely used methods for screening for kidney disease are an
analysis of a random urine sample for albuminuria and a serum creatinine
measurement to calculate an estimated glomerular filtration rate (GFR). It is
recommendable to use both of these methods as significant kidney disease can present
with diminished GFR or proteinuria, or both. (Garg AX et al 2002)

GFR is an indication of functioning kidney mass, the stages of chronic renal failure
are based on an estimated GFR:

Stage 1 GFR (ml per min per 1.73 m²) >89
Stage 2                           60-89
Stage 3                           30-59
Stage 4                            15-29
Stage 5                            <15 or dialysis


Significant kidney dysfunction may be present despite a normal serum creatinine
level. An estimated GFR based on serum creatinine level correlates better with direct
measures of the GFR and detects more cases of chronic kidney disease than does the
serum creatinine level alone.

Clinically useful GFR estimates are calculated from the measured serum creatinine
level after ajustments for age, sex and race. (Levey AS et al 1999; Cockcroft DW,
Gault MH 1976) The two most commonly used formulas for GFR estimation are the
MDRD (Modification of Diet in Renal Sisease) study equation and the Cockcroft-
Gault equation. Validation studies in middle-aged patients with chronic kidney
disease showed MDRD study equation to be more accurate. (Levey AS et al 1999).
However, the MDRD study equation was found to systematically underestimate the
GFR in patients without chronic kidney disease.( Rule AD et al 2004)

FORMULAS:

Abbreviated MDRD study equation12†
                                             -             -
GFR (mL per minute per 1.73 m2) = 186 X (SCr) 1.154 X (age) 0.203 X (0.742, if female) X (1.210, if black)

Cockcroft-Gault equation13
                             (140 - age) X weight
CCr (mL per minute) =                                X (0.85, if female)
                             72 X SCr
GFR = glomerular filtration rate; MDRD = Modification of Diet in Renal Disease; S Cr = serum creatinine
  concentration; CCr = creatinine clearance.
*-For each equation, SCr is in milligrams per deciliter, age is in years, and weight is in kilograms.
†-In validation studies,14-17 the MDRD study equation performed as well as versions with more variables; however, a
  recent study18 found that the equation underestimated the GFR in patients who did not have chronic kidney
  disease.


C (mL per minute) =(140 - age) X weight X (0.85, if female)
  Cr

                               0,81 X SCr
                  S   Cr   Micromol/L
In most situations and as long as kidney function is stable, a calculated GFR can
replace measurement of a 24-hour urine collection for creatinine clearance.
Determination of creatinine clearance using 24-hour urine collection is still required
in pregnant women, patients with extremes of age and weight, patients with
malnutrition, patients with skeletal muscle diseases, paraplegia or quadripülegia,
patients with a vegetarian diet and rapidly changuing kidney function. (Snyder S,
Pendergraph B 2005)


Detecting and quantitation of proteinuria are essential to the diagnosis and treatment
of chronic kidney disease. Albumin, the predominant protein excreted by the kidney
in most types of renal diseases, can be detected by urine dipstick testing. The protein-
creatinine ratio in an early-morning random urine sample correlates well with 24-hour
urine protein excretion and is much easier to obtain. (National Kidney Foundation
2002). Microalbuminuria often heralds the onset of diabetic nephropathy, therefore
screening for microalbuminuria is recommended for all patients at risk for kidney
disese. Screening can be performed using a microalbumin-sensitive dipstick or
analysis of a random morning urine sample to determine the microalbumin-creatinine
ratio.

Screening for the diseases that may lead to chronic kidney failure. The most important
reasons of chronic renal failure are diabetes and hypertension. Therefore early
detection of these diseases and appropriate treatment is a method of avoiding or
postponing complications, incl. chronic kidney failure. However, population-based
screening for diabetes has not been found as an effective approache for improving
diabetes outcomes. Screening of hypertension by measurement of blood pressure at
the office visits has found support in many guidelines.



Garg AX, Kiberd BA, Clark WF, Haynes RB, Clase CM. Albuminuria and renal
insufficiency prevalence guides population screening: results from the NHANES III.
Kidney Int 2002; 61:2165-75
Snyder S, Pendergraph B. Detection and evaluation of chronic kidney disease. Am
Fam Physician 2005;72:1723-34

Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N, Roth D. A more accurate
method to estimate glomerular filtration rate from serum creatinine: a new prediction
equation. Modification of Diet in Renal Disease Study Group. Ann Intern Med 1999;
130:461-70.
Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine.
Nephron 1976; 16:31-41

National Kidney Foundation. KEEP: Kidney Early Evaluation Program. Annual data
report. Program introduction. Am J Kidney Dis 2003; 42(5 suppl 4): S5-15;
McClellan WM, Ramirez SP, Jurkovitz C. Screening for chronic kidney disease:
unresolved issues. J Am Soc Nephrol 2003; 14 (7 suppl 2):S81-7.

Rule AD, Larson TS, Bergstrahl EJ, Slezak JM, Jacobsen SJ, Cosio FG. Using serum
creatinine to estimate glomerular filtration rate: accuracy in good health and in
chronic kidney disease. Ann Intern Med 2004; 141:929-37
National Kidney Foundation. K/DOQI, clinical practice guidelines for chronic kidney
disease: evaluation, classification and stratification. Am J Kidney Dis 2002; 39 (2
suppl 1): S1-266.

US Task Force….



Prevention

Main part of the total medical cost budget involves the treatment of CVD. Primary
and secondary prevention of cardiovascular and kidney disease remain the main
purpose in modern medicine as cardiovascular morality represents the main reason of
death in the world. The main cause of death in patients with CKD is cardiovascular
catastrophe and the risk to die is in ESRD patients even 10-20 times higher compared
with general population (13,14). Despite the magnitude of the resources committed to
the treatment of ESRD and the substantial improvements in the quality of dialysis
therapy, these patients continue to experience significant mortality and morbidity, and
a reduced quality of life. Therefore, CKD should be recognized as early as possible
and all prevention interventions that may arrest the kidney disease progression should
be used. Earlier stages of CKD can be detected through laboratory testing, and that
therapeutic interventions implemented early in the course of CKD
are effective in slowing or preventing the progression toward kidney failure and its
associated complications (15).
When kidney disease progresses CKD patients become hypertensive, have acquired
combined hyperlipidemia and hyperhomocysteinemia, increased oxidative stress, and
decreased physical activity and psychosocial stress. If patients choose to smoke, the
additive risk is profound (16). Diabetes mellitus is a major risk factor for both
cardiovascular disease and CKD progression (17). Moreover, CKD patients are
becoming older and are often menopausal if female (18). Finally, renal patients have a
dramatic tendency for vascular and cardiac calcification that is related with
hyperphosphatemia and secondary hyperparathyroidism (19). Also, the risk of
atherosclerotic cardiovascular diseases (CVD) in patients with CRF, especially in
patients on renal replacement therapy, has shown to be 10-20 times greater than in the
general population (14, 20).
The management of several renal and CVD risk factors as hypertension, overweight,
hypercholesterolemia, hypertriglyceridemia, and others should begin early in the
course of chronic renal insufficiency with reno- and vasoprotective medications (21).
In addition to classical risk factors such as age, male gender, smoking, hypertension,
diabetes and dyslipidemia, physical inactivity, which also exist in the general
population, patients with chronic renal failure have specific risk factors. Additional
specific risk factors for advanced CKD are various uraemic toxines,
hyperphosphatemia, severe prolonged oxidative stress, malnutrition, and
hyperuricemia and immunosupressive treatment. Psychosocial factors, such as
environmental stress and responsiveness to stress should not be unmentioned. The
approach to the risk factors should be guided by the principle that chronic renal
disease patients belong into the highest risk group for subsequent atherosclerotic
complications.

References

   1. Anderson, Brenner
   2. Ots M, Pechter U, Tamm A: Characteristics of progressive renal disease. Clin
       Chim Acta 2000;2971-2:29-41.
   3. Moeller S, Gioberge S, Brown G: ESRD patients in 2001: global overview of
       patients, treatment modalities and development trends. Nephrol Dial
       Transplant 2002;1712:2071-2076.
   4. Jager KJ, van Dijk PC. Has the rise in the incidence of renal replacement
       therapy in developed countries come to an end? Nephrol Dial Transplant
       2007;22:678-680
   5. U.S. Renal Data System, USRDS 2006 Annual Data Report: Atlas of End-
       Stage Renal Disease in the United States, National Institutes of Health,
       National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda,
       MD, 2006. Am J Kidney Dis 2006; 47(Suppl 1):S1.
   6. Locatelli F, D'Amico M, Cernevskis H, Dainys B, Miglinas M, Luman M, Ots
       M, Ritz E: The epidemiology of end-stage renal disease in the Baltic
       countries: an evolving picture. Nephrol Dial Transplant 2001;167:1338-1342.
   7. Gregorio T Obrador, Brian JG Pereira. Epidemiology of chronic kidney
       disease and screening recommendations. UpToDate 2007; 15
   8. http://www.musili.fi/fin/munuaistautirekisteri/
   9. K. Kõlvald,…. Renal replacement therapy trends in Estonia. Transplant Int
       2007:
   10. K/DOQI clinical practice guidelines for chronic kidney disease: evaluation,
       classification, and stratification. Am J Kidney Dis 2002; 39:S1.),
   11. Levey, AS, Eckardt, KU, Tsukamoto, Y, et al. Definition and classification of
       chronic kidney disease: A position statement from Kidney Disease: Improving
       Global Outcomes (KDIGO). Kidney Int 2005; 67:2089.
   12. Baigent C, Burbury K, Wheeler D: Premature cardiovascular disease in
       chronic renal failure. Lancet 2000;3569224:147-152.
   13. Coresh, J, Astor, BC, Greene, T, et al. Prevalence of chronic kidney disease
       and decreased kidney function in the adult US population: Third National
       Health and Nutrition Examination survey. Am J Kidney Dis 2003; 41:1.
   14. Foley RN, Parfrey PS, Sarnak MJ: Clinical epidemiology of cardiovascular
       disease in chronic renal disease. Am J Kidney Dis 1998;325 Suppl 3:S112-
       119.
   15. Pereira, BJG. Optimization of pre-ESRD care: The key to improved dialysis
       outcomes. Kidney Int 2000; 57:351.
   16. Orth SR, Ritz E: The renal risks of smoking: an update. Curr Opin Nephrol
       Hypertens 2002;115:483-488.
   17. Ritz E, Orth SR: Nephropathy in patients with type 2 diabetes mellitus. N Engl
       J Med 1999;34115:1127-1133.
   18. Shlipak MG, Simon JA, Grady D, Lin F, Wenger NK, Furberg CD: Renal
       insufficiency and cardiovascular events in postmenopausal women with
       coronary heart disease. J Am Coll Cardiol 2001;383:705-711.
   19. Amann K, Tornig J, Kugel B, Gross ML, Tyralla K, El-Shakmak A, Szabo A,
       Ritz E: Hyperphosphatemia aggravates cardiac fibrosis and microvascular
       disease in experimental uremia. Kidney Int 2003;634:1296-1301.
   20. Eknoyan G, Levey AS, Levin NW, Keane WF: The national epidemic of
       chronic kidney disease. What we know and what we can do. Postgrad Med
       2001;1103:23-29: quiz 28
   21. Meyer KB, Levey AS: Controlling the epidemic of cardiovascular disease in
       chronic renal disease: report from the National Kidney Foundation Task Force
       on cardiovascular disease. J Am Soc Nephrol 1998;912 Suppl:S31-42.
   22. Holley, JL, Nespor, SL. Nephrologist-directed primary health care in chronic
       dialysis patients. Am J Kidney Dis 1993; 21:628
   23. Schwartz, JS, Lewis, CE, Clancy, C, et al. Internists' practice in health
       promotion and disease prevention: A survey. Ann Intern Med 1991; 114:46.
   24. Zimmerman, DL, Selick, A, Singh, R, Mendelssohn, DC. Attitudes of
       Canadian nephrologists, family physicians and patients with kidney failure
       toward primary care delivery for chronic dialysis patients. Nephrol Dial
       Transplant 2003; 18:305.)
   25. Jean L Holley. The nephrologist as primary care physician in patients with
       end-stage renal disease. UpToDate 2007; 15
   26. Inglismaal tehtud töö NDT, 2007



Predialysis

Renal replacement therapy- role of primary care , internists and nephrologists

Availability of renal replacement therapy (RRT) forces the nephrologist to consider
its application in every patient in whom it might be indicated. As kidney disease
progresses patients cannot get help from family physician because of predialysis
activities and preparations to RRT. Patients can feel even that the nephrologist is the
only doctor who should manage all medical problems. Ideally, RRT is planned early
and each patient and clinical setting judged individually. Usually, specific predialysis
program takes several months and during this time CKD patients often visit dialysis
center.
There are many clinical problems in patients with CKD during predialysis and RRT
period that can be associated with CKD but not always. Therefore, nephrologists often
provide primary care or nonrenal related medical care to predialysis or to patients
undergoing chronic haemodialysis because patient visits the center often. The
nephrologist is the first who makes diagnose for instance of acute illness. Evidence
shows that many patients do not have even family physician and patients often feel
also that the nephrologist should manage their acute illness. On the other hand,
comparison of HD and CAPD patients PD patients less depended upon their
nephrologists (22).
A paucity of objective data exists concerning the nephrologist's role as a primary care
provider. Several studies suggest that the volume and type of practice provided by the
nephrologist for patients with ESRD may be similar to that of the primary care
practitioner (23,24,25). The problem is that if CKD patient numbers increases then in
many places may be lack of nephrologists who have time and also experience to
manage all medical problems in their RRT patients. It is probably true that patient
outcome may be influenced by the expertise of the physician but no studies have been
focused on the topic to compare outcome data of CKD populations managed only
with specialist and both with specialist together with internist


References

       1. Anderson, Brenner
       2. Ots M, Pechter U, Tamm A: Characteristics of progressive renal disease.
           Clin Chim Acta 2000;2971-2:29-41.
       3. Moeller S, Gioberge S, Brown G: ESRD patients in 2001: global overview
           of patients, treatment modalities and development trends. Nephrol Dial
           Transplant 2002;1712:2071-2076.
       4. Jager KJ, van Dijk PC. Has the rise in the incidence of renal replacement
           therapy in developed countries come to an end? Nephrol Dial Transplant
           2007;22:678-680
       5. U.S. Renal Data System, USRDS 2006 Annual Data Report: Atlas of End-
           Stage Renal Disease in the United States, National Institutes of Health,
           National Institute of Diabetes and Digestive and Kidney Diseases,
           Bethesda, MD, 2006. Am J Kidney Dis 2006; 47(Suppl 1):S1.
       6. Locatelli F, D'Amico M, Cernevskis H, Dainys B, Miglinas M, Luman M,
           Ots M, Ritz E: The epidemiology of end-stage renal disease in the Baltic
           countries: an evolving picture. Nephrol Dial Transplant 2001;167:1338-
           1342.
       7. Gregorio T Obrador, Brian JG Pereira. Epidemiology of chronic kidney
           disease and screening recommendations. UpToDate 2007; 15
       8. http://www.musili.fi/fin/munuaistautirekisteri/
       9. K. Kõlvald,…. Renal replacement therapy trends in Estonia. Transplant Int
           2007:
       10. K/DOQI clinical practice guidelines for chronic kidney disease:
           evaluation, classification, and stratification. Am J Kidney Dis 2002;
           39:S1.),
       11. Levey, AS, Eckardt, KU, Tsukamoto, Y, et al. Definition and classification
           of chronic kidney disease: A position statement from Kidney Disease:
           Improving Global Outcomes (KDIGO). Kidney Int 2005; 67:2089.
       12. Baigent C, Burbury K, Wheeler D: Premature cardiovascular disease in
           chronic renal failure. Lancet 2000;3569224:147-152.
       13. Coresh, J, Astor, BC, Greene, T, et al. Prevalence of chronic kidney
           disease and decreased kidney function in the adult US population: Third
           National Health and Nutrition Examination survey. Am J Kidney Dis
           2003; 41:1.
       14. Foley RN, Parfrey PS, Sarnak MJ: Clinical epidemiology of
           cardiovascular disease in chronic renal disease. Am J Kidney Dis
           1998;325 Suppl 3:S112-119.
       15. Pereira, BJG. Optimization of pre-ESRD care: The key to improved
           dialysis outcomes. Kidney Int 2000; 57:351.
       16. Orth SR, Ritz E: The renal risks of smoking: an update. Curr Opin Nephrol
           Hypertens 2002;115:483-488.
       17. Ritz E, Orth SR: Nephropathy in patients with type 2 diabetes mellitus. N
           Engl J Med 1999;34115:1127-1133.
       18. Shlipak MG, Simon JA, Grady D, Lin F, Wenger NK, Furberg CD: Renal
           insufficiency and cardiovascular events in postmenopausal women with
           coronary heart disease. J Am Coll Cardiol 2001;383:705-711.
       19. Amann K, Tornig J, Kugel B, Gross ML, Tyralla K, El-Shakmak A, Szabo
           A, Ritz E: Hyperphosphatemia aggravates cardiac fibrosis and
           microvascular disease in experimental uremia. Kidney Int 2003;634:1296-
           1301.
       20. Eknoyan G, Levey AS, Levin NW, Keane WF: The national epidemic of
           chronic kidney disease. What we know and what we can do. Postgrad Med
           2001;1103:23-29: quiz 28
       21. Meyer KB, Levey AS: Controlling the epidemic of cardiovascular disease
           in chronic renal disease: report from the National Kidney Foundation Task
           Force on cardiovascular disease. J Am Soc Nephrol 1998;912 Suppl:S31-
           42.
       22. Holley, JL, Nespor, SL. Nephrologist-directed primary health care in
           chronic dialysis patients. Am J Kidney Dis 1993; 21:628
       23. Schwartz, JS, Lewis, CE, Clancy, C, et al. Internists' practice in health
           promotion and disease prevention: A survey. Ann Intern Med 1991;
           114:46.
       24. Zimmerman, DL, Selick, A, Singh, R, Mendelssohn, DC. Attitudes of
           Canadian nephrologists, family physicians and patients with kidney failure
           toward primary care delivery for chronic dialysis patients. Nephrol Dial
           Transplant 2003; 18:305.)
       25. Jean L Holley. The nephrologist as primary care physician in patients with
           end-stage renal disease. UpToDate 2007; 15
       26. Inglismaal tehtud töö NDT, 2007



Concomitant major health problems in CKD patients (infections, nutrition,
anaemia)

Infection

        The more common pathogenic viral infections in chronic kidney disease
(CKD) are cytomegalovirus, HIV-1, hepatitis C virus and parvovirus B19. Infectious
diseases are the second most common cause of death in end-stage renal disease
(ESRD) patients. (1,2)
        Among a representative sample of the US population, hepatitis C is
independently associated with albuminuria among adults over the age of 40; however,
it does not seem to be significantly associated with a low eGFR in this population-
based cross-sectional analysis. (3) Hepatitis C also is a complicating factor among
patients with end-stage renal disease and renal transplants. The source of HCV
infection in these patients can be nosocomial. Screening and careful attention to
infection control precautions are mandatory for dialysis units to prevent the spread of
hepatitis C (12). Infection with parvovirus B19 causes several clinical syndromes
(fifth disease, transient aplastic crisis, pure red cell aplasia, and hydrops fetalis) and
may contribute to other illnesses. (4) Human immunodeficiency virus (HIV)-infected
patients can develop different types of chronic kidney disease (CKD). The most
common histological finding of renal biopsy is HIV-associated nephropathy
(HIVAN). HIVAN is now the third most common cause of end stage renal failure
(ESRF) (after diabetes mellitus and hypertension) in African-Americans aged 20–64
years. With the improved survival after the use of highly active antiretroviral therapy
(HAART) in HIV-infected patients, there are increasing reports of development of
CKD and ESRF in this population. (5) All patients at the time of human
immunodeficiency virus (HIV) diagnosis should be assessed for existing kidney
disease with a screening urine analysis for proteinuria and a calculated estimate of
renal function. Additional evaluations (including quantification of proteinuria, renal
ultrasound, and potentially renal biopsy) and referral to a nephrologist are
recommended for patients with proteinuria of grade >1+ by dipstick analysis or
glomerular filtration rate (GFR) <60 mL/min per 1.73 m2 (6)
        Regardless of age and the presence of other comorbid illnesses, it is
recommended that patients with chronic kidney disease receive regular vaccination.
Hepatitis B is one of the most serious infectious diseases in the world. The virus can
be transmitted among high-risk groups including CKD patients. HBV vaccination in
patients with kidney disease remains highly recommendable. Hepatitis A virus
vaccination among the general population has been used for decades. HAV
vaccination in ESRD patients is well tolerated and immunogenic. Varicella may be
severe and fatal infection in immunocompromised ESRD children. Varicella
vaccination is safe and effective in ESRD patients and is thus recommended in these
patients. Influenza is a common infection among CKD patients. Several studies
showed that influenza vaccination was safe and effective in patients with CKD despite
an impaired antibody response. In conclusion, influenza vaccination is highly
recommended among ESRD patients. ESRD patients should thus receive
Haemophilus influenza type B vaccine at the same doses as for healthy subjects. All
children should be treated with measles, mumps and rubella vaccines (MMR),
including dialysis patients. Diphtheria and tetanus infections can be prevented by
using vaccines in ESRD patients. Pneumococcal vaccination is thus recommended in
CKD patients with standard doses of 23-valent pneumococcal polysaccharide vaccine,
but revaccination should be performed within 3–5 years. Live vaccines (yellow fever,
polio, varicella and MMR vaccines) are generally avoided because they present a
theoretical risk of vaccine-induced infection. (7)

Infection after transplantation

        Infections remain the second most common cause of death in kidney
transplant recipients. The risk for infection in these patients is determined primarily
by the intensity of exposure to potential pathogens and the net state of
immunosuppression. (8) Overall, the most prevalent opportunistic infections are viral,
and CMV is the primary virus involved. CMV is the most common viral infection in
the transplant population. CMV causes 2 major types of problems: direct effects,
such as CMV syndrome and tissue invasive disease; and indirect effects, such as acute
and chronic rejection, super-infections, cardiac complications, diabetes, and
lymphoma. CMV infection and disease have been reported to be independent risk
factors for acute renal allograft rejection. (9) Drugs that prevent CMV, either
valacyclovir (10) or ganciclovir (11) or both, decrease the incidence of acute
rejection. However, a host of community-acquired and opportunistic bacterial, viral,
and fungal infections may occur at different rates depending on the period after
transplantation. To reduce the burden of infection-related morbidity and mortality,
patient vaccination status should be reviewed at the first clinic visit, and a vaccination
strategy should be developed, keeping in mind that live vaccines are not given after
transplantation and that patients, close contacts, and family members should receive
injectable influenza vaccine yearly (inhaled influenza vaccine should not be given to
transplant recipients or family members). Pneumococcal polysaccharide vaccine
should be administered before transplantation and repeated every 3 to 5 yr after initial
vaccination. Vaccination series should be restarted approximately 6 mo after
transplantation, and efficacy should be documented by serologic assays when
available. Finally, adult travelers after kidney transplantation need appropriate
counseling and vaccinations before their tri). (8)




References:

1. LeslieA.Bruggeman // Viral Subversion Mechanisms in Chronic Kidney Disease
Pathogenesis // Clin. J. Am. Soc. Nephrol., Jul 2007; 2: S13 - S19.
2. Foley RN. // Infections in patients with chronic kidney disease // Infect Dis Clin
North Am. 2007 Sep;21(3):659-72.
3. Judith I. Tsui, Eric Vittinghoff, Michael G. Shlipak, and Ann M. O‘Hare //
Relationship between Hepatitis C and Chronic Kidney Disease: Results from the
Third National Health and Nutrition Examination Survey // J. Am. Soc. Nephrol., Apr
2006; 17: 1168 - 1174.
4. Meryl Waldman and Jeffrey B. Kopp // Parvovirus B19 and the Kidney // Clin. J.
Am. Soc. Nephrol., Jul 2007; 2: S47 - S56.
5. Chi Yuen Cheung, Kim Ming Wong, Man Po Lee, Yan Lun Liu, Heidi Kwok, Rita
Chung, Ka Foon Chau, Chung Ki Li, and Chun Sang Li // Prevalence of chronic
kidney disease in Chinese HIV-infected patients // Nephrol. Dial. Transplant., Nov
2007; 22: 3186 - 3190.
6. Gupta SK, Eustace JA, Winston JA, Boydstun II, Ahuja TS, Rodriguez RA,
Tashima KT, Roland M, Franceschini N, Palella FJ, Lennox JL, Klotman PE,
Nachman SA, Hall SD, Szczech LA. Guidelines for the management of chronic
kidney disease in HIV-infected patients: recommendations of the HIV Medicine
Association of the Infectious Diseases Society of America. Clin Infect Dis 2005 Jun
1;40(11):1559-85.
7. Nicolas Janus, Launay-Vincent Vacher, Svetlana Karie, Elena Ledneva, and Gilbert
Deray // Vaccination and Chronic Kidney Disease// Nephrol. Dial. Transplant., Dec
2007; 10.1093/ndt/gfm851.
8. Arjang Djamali, Millie Samaniego, Brenda Muth, Rebecca Muehrer, R. Michael
Hofmann, John Pirsch, Andrew Howard, Georges Mourad, and Bryan N. Becker //
Medical Care of Kidney Transplant Recipients after the First Posttransplant Year //
Clin. J. Am. Soc. Nephrol., Jul 2006; 1: 623 - 640.
9. Sageda S, Nordal KP, Hartmann A, et al. The impact of cytomegalovirus infection
and disease on rejection episodes in renal allograft recipients. Am J Transplant.
2002;2:850-856.
10. Lowance D, Neumayer HH, Legendre CM, et al. Valacyclovir for the prevention
of cytomegalovirus disease after renal transplantation. N Engl J Med. 1999;340:1462-
1470.
11. Ricart MJ, Malaise J, Moreno A, Crespo M, Fernandez-Cruz L. Cytomegalovirus:
occurrence, severity, and effect on graft survival in simultaneous pancreas-kidney
transplantation. Nephrol Dial Transplant. 2005;20(suppl 2):ii25-ii32, ii62.
12. CM Meyers, LB Seeff, CO Stehman-Breen // Hepatitis C and renal disease: an
update. // Am J Kidney Dis. 2003 Oct;42(4):631-57


Nutrition

        Dietary recommendation is important in management of CKD and the
maintenance of broader health in CKD patients. Malnutrition is a frequent finding in
ESRF, affecting 30-40% of patients. About 10% of patients on maintenance dialysis
show signs of severe malnutrition. (1). Family physicians will be mostly efficient at
the stage of malnutrition prevention, by implementing an early, interactive dietary and
nutritional care programs in close collaboration with specialized dietitians.
        Extensive European (2,3) and US (4,11) guidelines on the assessment of
nutrition in renal patients are available. All patients with stage 4-5 CKD should
undergo regular nutritional screening. Nutritional assessment should include a
minimum of a record of body weight prior to onset of ill health (well weight), current
body weight and ideal body weight; body mass index (weight/height2); subjective
global assessment, based on either a 3- or 7-point scale. Other measures of nutritional
state are: serum creatinine, serum lipids, serum albumin and handgrip strength. If a
patient has GFR < 30 ml/min per 1.73 m2, then his/her nutritional status should be
monitored by measuring body weight and serum albumin every three months. (9)
There is no single ‗gold standard‘ measure of nutritional state. Therefore a panel of
measurements should be used, reflecting the various aspects of protein-calorie
nutrition.
        The dietary recommendations are different in all countries, but all guidelines
agree that the energy intake in CKD patients is 35 kcal/kg/day and 30 kcal/kg/day
may be sufficient in those over the age of 60. Sodium, total fat, cholesterol,
carbohydrate, protein, phosphorus, potassium are restricted for CKD patients (1
table).

Table 1. Macronutrient Composition and Mineral Content of the Dietary Approaches
to Stop Hypertension (DASH) Diet Recommended by JNC 7, with Modification for
Stages 3–4 of CKD (11)
Nutrient                            Stage 1 – 2 of CKD Stage 3 – 4 of CKD
Sodium (g/d)*                       < 2,4                   < 2,4
Total fat (% of calories)           < 30                    < 30
Saturated fat (% of calories)       < 10                    < 10
Cholesterol (mg/d)                  < 200                   < 200
Carbohydrate (% of calories)**      50 – 60                 50 – 60
Protein (g/kg/d, % of calories)     1,4 (18)                0,6 – 0,8 (10)
Phosphorus (g/d)                    1,7                     0,8 – 1,0
Potassium (g/d)                     >4                      2-4
*Not recommended for patients with ―salt-wasting‖
**Adjust so total calories from protein, fat and carbohydrate is 100 %

      The effects of dietary protein restriction are controversial. A meta-analysis in
1996 concluded that this intervention reduces proteinuria and slows the rate of the
progression by reducing the rate of decline of GFR.(5) A later meta-analysis
concluded that effects were less in RCTs than in non-RCT studies, that the effect was
relatively greater in patients with diabetes, and that the magnitude of the effect was
relatively weak. A Cochrane review, last updated in 1997 and not confined to RCTs,
concluded that reducing protein intake does appear to slow progression of
nephropathy in type 1 diabetes, but identified several unanswered questions: the level
of protein restriction that should be used, whether compliance could be expected in
routine care, and whether improvement in intermediate outcomes (eg creatinine
clearance) would translate into improved clinical outcomes.(6) Since those reports an
RCT confined to patients with type 2 diabetes and nephropathy has reported negative
effects,(7) but an RCT in type 1 patients suggested a reduction in mortality.(8)
        Accordingly, the K/DOQI guidelines have recommended that CKD patients
(GFR < 25 ml/min) receive a diet providing 0.6 g/kg of desirable body weight (DBW)
per day of proteins (11), while others suggest that the protein content of the diet
should not be lower than 0.75 g/kg/day, and should not exceed 0.8–1.0 g/kg/day (12–
16). Diets with <0.55 g/kg/day of proteins are strongly discouraged, for the risk of
protein malnutrition (17). Some studies advocate that the reduction in protein intake
below 0.8 g/kg/day in patients with advanced renal failure should be considered a
criterion for starting dialysis therapy (16).
        Data of the last good quality study suggest that the 0.55 g/day diet guarantees a
better metabolic control, as mirrored by the less frequent use of drugs, and it is not
associated with a risk of malnutrition. (17)

   1. D Fouque and F Guebre-Egziabher // An update on nutrition in chronic kidney
       disease. // Int Urol Nephrol, January 1, 2007; 39(1): 239-46.
   2. Clinical Practice Guidelines for the Care of Patients with Chronic Kidney
       Disease // UK Renal Association Clinical Practice Gudelines 4th Edition 2007
       //www.renal.org/guidelines
   3. Denis Fouque, Marianne Vennegoor, Piet Ter Wee // EBPG Guideline on
       Nutrition // Nephrol. Dial. Transplant., May 2007; 22: ii45 - ii87.
   4. American Dietetic Association. Chronic kidney disease (non-dialysis) medical
       nutrition therapy protocol. Chicago (IL): American Dietetic Association; 2002
       May.
   5. Pedrini MT, Levey AS, Lau J, Chalmers TC, Wang PH. The effect of dietary
       protein restriction on the progression of diabetic and nondiabetic renal
       diseases: a meta-analysis. Ann Intern Med 1996;124: 627–32.
   6. Waugh NR, Robertson AM. Protein restriction for diabetic renal disease.
       Cochrane Database Syst Rev 2000;(2):CD002181.
   7. Pijls LT, de Vries H, van Eijk JT, Donker AJ. Protein restriction, glomerular
       filtration rate and albuminuria in patients with type 2 diabetes mellitus: a
       randomized trial. Eur J Clin Nutr 2002;56:1200–7.
   8. Hansen HP, Tauber-Lassen E, Jensen BR, Parving HH. Effect of dietary
       protein restriction on prognosis in patients with diabetic nephropathy. Kidney
       Int 2002;62:220–8.
   9. W. Kline Bolton // Renal Physicians Association Clinical Practice Guideline:
       Appropriate Patient Preparation For Renal Replacement Therapy: Guideline
       Number 3 // J Am Soc Nephrology, 14: 1406–1410, 2003
   10. Chronic Kidney Disease 2006: A Guide to Select NKF-KDOQI Gudelines and
       Recommendation www.kidney.org/professionals/kls/pdf/Pharmacist_CPG.pdf
   11. National Kidney Foundation. K/DOQI Clinical Practice Guidelines for
       nutrition in chronic renal failure. Am J Kidney Dis (2000) 35:S56–S57.
   12. CARI. Caring for Australian with Kidney Impairment. In: Chronic Kidney
       Disease. Nutrition and Growth in Kidney Disease Guidelines.
       http://www.cari.org.au/ckd_nutrition_list_updating.php.
   13. Prichard S. Clinical Practice Guidelines of the Canadian Society of
       Nephrology for the treatment of patients with chronic renal failure: a re-
       examination. Contrib Nephrol (2003) 140:163–169.
   14. Cianciaruso B, Barsotti G, Oldrizzi L, Gentile MG, Del Vecchio L. Italian
       Society of Nephrology. Conservative therapy Guidelines for chronic renal
       failure. G Ital Nefrol (2003) 20(Suppl 24):48–60.
   15. The UK CKD Guidelines (2005) on the Renal Association website:
       http://www.renal.org/CKDguide/ckd.html.
   16. Churchill DN, Blake PG, Jindal KK, Toffelmire EB, Goldstein MB.
       Guidelines for Treating Patients with CRF. Chapter 1: Clinical Practice
       Guidelines for Initiation of Dalysis. J Am Soc Nephrol (1999) 10:S287–S321.
   17. Bruno Cianciaruso, Andrea Pota, Antonio Pisani, Serena Torraca, Roberta
       Annecchini, Patrizia Lombardi, Alfredo Capuano, Paola Nazzaro, Vincenzo
       Bellizzi, and Massimo Sabbatini // Metabolic effects of two low protein diets
       in chronic kidney disease stage 4–5—a randomized controlled trial //
       Nephrol. Dial. Transplant., doi:10.1093/ndt/gfm576



Anaemia

        Anemia is an early and common complication of chronic kidney disease. (1)
The prevalence of anemia varies with the degree of renal impairment in predialysis
patients with CKD, but once end-stage kidney failure occurs, all patients are
eventually affected. In the NHANES III (the Third National Health and Nutrition
Examination Survey) study (2), only 1% of participants with a glomerular filtration
rate (GFR) > 60 ml/min were found to suffer from anaemia [as defined in this study
as a haemoglobin (Hb) concentration <12 g/dl in men or <11 g/dl in women].
However, in a cohort of patients with CKD, 25% of patients with a GFR >50 ml/min
had Hb <12 g/dl (2). CKD patient categories with diabetes mellitus, congestive heart
failure, diseases e.g. vasculitis, lupus erythematosus, advanced age, kidney
transplantation are at high risk for anaemia development and should receive a greater
level of attention. (3)
         According representative meta-analysis compared with Hb values of >130
g/L or more in the CKD population with cardiovascular disease, Hb values of <120
g/L were associated with lower all-cause mortality. Hb values of 100 g/L or less
reduced the risk of hypertension, but increased the risk of seizures. From the available
trial evidence, in CKD patients with cardiovascular disease, the benefits associated
with higher Hb targets (reduced seizures) are outweighed by the harms (increased risk
of hypertension and death). (4) Because anaemia is an early complication of CKD,
patients with a GFR <60 ml/min/1.73 m2 should have their Hb level checked, and if
found to be low then their anaemia should be further investigated and treated, as
recommended by international guidelines (European Best Practice Guidelines (EBPG)
or K/DOQI clinical practice guidelines) (5,7).
        Family physician role in assessment of anaemia should involve laboratory
measurement of the following parameters: haemoglobin (Hb) concentration (to assess
the degree of anaemia), mean corpuscular volume (MCV) and mean corpuscular Hb
(MCH) (to assess the type of anaemia), absolute reticulocyte count (to assess
erythropoietic activity), plasma/serum ferritin concentration (to assess iron stores),
plasma/serum C-reactive protein (CRP) (to assess inflammation), assessment of occult
gastrointestinal blood loss (to assess possibility of gastrointestinal bleeding). This is
the basic patient evaluation and family physician usually can treat of most causes of
anaemia. Fuller investigations can be done by specialist (hematologist or
nephrologists).
        The Hb levels at which therapy with erythropoiesis-stimulating
agents (ESAs) should be initiated, as well as its target Hb level, remain
controversial (6). The EBPG recommend Hb values >11 g/dl (5), while the
K/DOQI clinical practice guidelines and clinical practice recommendations
suggest Hb levels between 11 and 13 g/dl (7). The use of a target
hemoglobin level of 13.5 g per deciliter (as compared with 11.3 g per
deciliter) was associated with increased risk and no incremental
improvement in the quality of life.(8) Recent trials recommend a target Hb
level between 11 and 12 g/dl in CKD patients. (8,9)



   1. Kazmi WH, Kausz AT, Khan S, et al. Anemia: An Early Complication of
      Chronic Renal Insufficiency. Am J Kidney Dis (2001) 38:803–812.
   2. Hsu CY, McCulloch CE, Curhan GC. Epidemiology of anemia associated
      with chronic renal insufficiency among adults in the United States: results
      from the third national health and nutrition examination survey. J Am Soc
      Nephrol (2002) 13:504–510.
   3. W. H. Hörl, Y. Vanrenterghem, P. Aljama, P. Brunet, R. Brunkhorst, L.
      Gesualdo, I. Macdougall, C. Wanner, and B. Wikström // OPTA: Optimal
      treatment of anaemia in patients with chronic kidney disease (CKD) //
      Nephrol. Dial. Transplant., June 2007; 22: iii20 - iii26
   4. G. F.M. Strippoli, J. C. Craig, C. Manno, and F. P. Schena
      Hemoglobin Targets for the Anemia of Chronic Kidney Disease: A Meta-
      analysis of Randomized, Controlled Trials // J. Am. Soc. Nephrol.,
      December 1, 2004; 15(12): 3154 - 3165.
   5. Locatelli F, Aljama P, Barany P, et al. Revised European best practice
      guidelines for the management of anaemia in patients with chronic renal
      failure. Nephrol Dial Transplant (2004) 19(Suppl 2):ii1–47.
   6. Remuzzi G, Ingelfinger JR. Correction of anaemia – payoffs and problems. N
      Engl J Med (2006) 355:2141–2146.
   7. K/DOQI clinical practice guidelines and clinical practice recommendations for
      anemia in chronic kidney disease in adults: Am J Kidney Dis. (2006)
      47([Suppl 3]):S11–S145.
   8. Singh AK, Szczech L, Tang KL, et al. Correction of anemia with epoetin alfa
      in chronic kidney disease. N Engl J Med (2006) 16:2085–2098.
   9. Drueke TB, Locatelli F, Clyne N, et al. Normalization of hemoglobin level in
      patients with chronic kidney disease and anemia. N Engl J Med (2006)
      16:2071–2084.
Education and guidelines




Quality of care in CKD



Shared care, referrals




Recommendations, issues for policy makers

Topics for discussion

Best practice examples


References

Appendices