Kidney failure stage 3 kidney disease life expectancy

December 25, 2018

Kidney disease leads to a reduction in life expectancy. How much of a reduction? It depends on several factors, especially a person’s age, sex, and the stage of the disease. Questions like these were first answered less than a decade ago. But thanks to an enormous amount of research, doctors now have an excellent picture of the prognosis for kidney disease.

Nevertheless, it’s important to keep in mind, every person is different—not just in terms of personality, but in terms of genetics, current health condition, and so forth. Life expectancy estimates can make no guarantees, but they may provide you with a general outlook.

The Stages of Kidney Disease

How many stages of kidney disease are there? It’s a little complicated. While there are five primary stages of kidney diseases, the third stage can be broken into two sub-stages. Each stage is determined by measuring glomerular filtration rate (GFR), which is used to indicate how well the kidneys are functioning.

Stage 1 and 2: Early Warnings

Stage 1 indicates a person with normal GFR at or above 90mL/min. The second stage is indicated by GFR between 60-89mL/min, which is when minor symptoms tend to start. In these stages, kidney disease can be caught before it has done any significant damage.

Stage 3, 4, and 5: Nearing Kidney Failure

It’s stage 3 that defines the point at which mortality becomes a greater concern than the likelihood of developing end-stage renal disease. With kidney function reduced between 59-30mL/min, the previously minor symptoms of stage 2 become far more severe. From the end of stage 3, there are only 15-points of kidney function standing between entering stage 5, which indicates total kidney failure.

Life Expectancy by Sex

As much as anything else, life expectancy for kidney disease depends on a person’s age and sex.

For a 60-year-old man, stage 1 kidney disease life expectancy will be approximately 15 years. That figure falls to 13 years, 8 years, and 6 years in the second, third, and fourth stages of kidney disease respectively. For a 60-year old woman, stage 1 life expectancy is 18 years, while stage 2 is only one year less. For stage 3 kidney disease, her life expectancy would be 11 years.

In short, women have a slightly greater life expectancy at all ages. But during stages 4 and 5, those advantages slip away, and life expectancy becomes essentially identical between the sexes.

Life Expectancy by Age

Age changes everything. Consider the life expectancy of 70-year old men and women. For a 70-year old man, his life expectancy for the first four stages of kidney disease would be 9 years, 8 years, 6 years, and 4 years respectively.

For a 70-year-old woman, life expectancy is 11 years, 8 years, and 4 years. Once again, women start with a greater life expectancy, but the differences disappear in later stages of the disease.

Stage Five

Stage 5 kidney disease means total kidney failure and the necessity of dialysis. Five decades ago, a failed kidney meant death was likely. These days, things are quite a bit different. According to the National Kidney Foundation, the average life expectancy for a patient on dialysis is 5-10 years. Though for someone between the ages of 70 and 74, life expectancy is closer to four years on dialysis.

Keeping Healthy Kidneys

Age and health problems can impair your ability to endure kidney disease. While there’s no cure, there are things you can to do learn to manage kidney disease.

If there’s one thing this data should make clear, it’s that taking some simple steps to prevent the progression of kidney disease won’t only preserve health, but it can help save years of life.

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  • Br J Gen Pract
  • v.60(575); June 2010
  • PMC2887275

Br J Gen Pract. 2010 Jun 1; 60(575): e266–e276.

Keith McCullough, MRCP, Specialist Registrar in Nephrology

Aberdeen Royal Infirmary Renal Unit, NHS Grampian, Aberdeen

Graham Scotland, BSc, MSc, Research Fellow and Paul McNamee, BA, MSc, PhD, Senior Research Fellow

Health Economics Research Unit, University of Aberdeen, Aberdeen

Gordon Prescott, BSc, MSc, PhD, CStat, Senior Lecturer in Medical Statistics and Alison MacLeod, MRCP, MD, Professor of Medicine and Pharmacology

Health Economics Research Unit, University of Aberdeen, Aberdeen

Nick Fluck, MRCP, MD, Consultant Nephrologist

Aberdeen Royal Infirmary Renal Unit, NHS Grampian, Aberdeen

William Cairns Smith, PhD, MD, MRCP, FFPH, Clinical Professor of Public Health and Corri Black, BSc, MSc, MRCP, FFPH, Senior Clinical Lecturer

Health Economics Research Unit, University of Aberdeen, Aberdeen

Abstract

Background

Stage-3 chronic kidney disease (CKD) is the first stage that is identifiable from a blood test alone. In the UK, it accounts for the majority of people on primary care CKD registers. It also represents a group of people who, in the past, would have gone unnoticed clinically. In order to support patients and plan services, the natural history of stage-3 CKD is important.

Aim

To systematically review the natural history of stage-3 CKD in order to describe all cause mortality, cardiovascular morbidity and mortality, and renal outcomes.

Design of study

Systematic review of the literature.

Method

MEDLINE and Embase databases were searched from 1998 to February 2009. Systematic reviews and cohort studies that included adults with stage-3 CKD were considered eligible. Studies were appraised and data extracted by one reviewer and checked by a second.

Results

Thirteen studies were identified including a total of 728 328 people. The all-cause mortality rate varied from 6% in 3 years to 51% in 10 years and was higher in stage-3B CKD (4.8 per 100 person-years) than stage-3A CKD (1.1 per 100 person-years). The relative risk of mortality (all-cause mortality or cardiovascular disease [CVD] mortality) was higher in stage-3 CKD compared with no CKD, but the increase was small for those with stage-3A CKD (hazard ratio [HR] 1.2–1.7) and greater in stage 3B (HR 1.8–3.3). End-stage renal disease was rare (4% in 10 years) and renal progression was evident in <20% of patients after 5 years.

Conclusions

For patients with stage-3 CKD, risk of mortality was higher than for those without CKD, but the risk of progression was low. CKD registers provide an opportunity for GPs to assess the risk of patients developing CVD.

Keywords: chronic kidney disease, natural history, primary care, systematic review

INTRODUCTION

With prevalence studies currently estimating that around 5% of the adult population will have evidence of stage-3 or ‘moderate’ chronic kidney disease (CKD),1–7 the last 5 years has seen CKD become a major healthcare challenge. Commentators have described CKD as a ‘major public health problem’ and talked of an ‘epidemic’.8–10 Although there is some evidence that the prevalence in CKD is increasing, the change in epidemiology is essentially driven by an increase in detection and awareness.11

In 2002, the US Kidney Disease Outcomes Quality Initiative (KDOQI) proposed a definition of CKD with five stages that has been adopted internationally: ‘kidney damage or decreased kidney function (glomerular filtration rate [GFR] <60 mL/min/1.73 m2) for ≥3 months’ (Table 1).12,13 Those with GFR ≥60 mL/min/1.73 m2 (Stage 1–2) are considered to have CKD if they presented with kidney damage as defined by pathological abnormalities or markers of damage. In the UK, and elsewhere, this new definition has been accompanied by changes to improve the consistency of laboratory reporting, making it easier for clinicians to recognise impairment in kidney function.14 The addition of CKD management to the Quality and Outcomes Framework (QOF) in 2006 encouraged GPs who were responsible for the care of the majority of people with CKD to identify those with GFR <60 mL/min/1.73 m2 (stage-3 CKD or worse) and record them on a practice register. Proactive management of blood pressure and use of angiotensin converting enzyme (ACE) inhibitors or angiotensin receptor blockers is also supported in the QOF and clinical guidelines.15,16 Internationally, similar opportunistic detection has been implemented and some countries or communities have introduced screening of groups who are at high risk of developing CKD.17,18

Table 1

Kidney Disease Outcomes Quality Initiative definition of chronic kidney disease (modified by the UK Renal Consensus conference to split stage 3 into two subgroups).12,13

CKD stageDefinition (chronicity defined by presence of abnormality for ≥3 months)
Stage 1 Kidney damage with normal or raised GFR (≥90 mL/min/1.73 m2)
Stage 2 Kidney damage with mildly impaired GFR (60–89 mL/min/1.73 m2)
Stage 3A Moderately impaired GFR (45–59 mL/min/1.73 m2)
Stage 3B Moderately impaired GFR (30–44 mL/min/1.73 m2)
Stage 4 Severely impaired GFR (15–29 mL/min/1.73 m2)
Stage 5 End-stage renal failure or GFR <15 mL/min/1.73 m2

Stage-3 CKD is the first stage that can be identified from a blood test alone, and accounts for the vast majority of people now being detected and labelled with CKD on general practice disease registers. In every 10 000 adult patients in primary care, an estimated 144 new patients will be detected each year with stage-3 CKD, as compared with three in stage 4 and 0.3 in stage 5.19 Stage-3 CKD also represents those people who would previously have gone unnoticed clinically, people who reflect a very different population than those diagnosed as having CKD and attending nephrology clinics in the past. In stages 4 and 5, the clinical significance of CKD is well understood, with many individuals experiencing symptoms and complications (hypertension, anaemia, undernutrition, renal bone disease, and metabolic acidosis) as well as an increased risk of cardiovascular disease (CVD), all-cause mortality and end-stage renal disease (ESRD) requiring renal replacement therapy (RRT).14,15 In stage 3, the clinical implications for the future health of the patient are less clear.20,21

In order to support patients, plan services, evaluate cost-effectiveness and develop policies, it is critical that the natural history of stage-3 CKD is understood. This article systematically reviews the natural history of stage-3 CKD in terms of mortality and renal outcomes.

METHOD

Search strategy

A systematic review of the published literature was conducted, searching the MEDLINE and Embase databases for studies dating from 1998 to February 2009. A combination of medical subject headings and text terms were used for ‘chronic kidney disease’ and ‘natural history’ (Table 2). A manual search of reference lists from included studies was carried out. Searches were restricted to English language.

Table 2

Example search strategy for MEDLINE (modified for Embase).

SearchSearch term
1 Exp *Kidney Failure, Chronic/
2 (Renal or kidney or nephropath$ or nephrolog$).tw.
3 CKD.tw.
4 Exp *Natural History/
5 Exp Disease Progression/
6 Natural course.tw.
7 Disease course.tw.
8 (Cohort or follow-up or follow-up or longitudinal or prospective or screening or cross sectional or cross-sectional).tw.
9 Population-based stud$.tw.
10 Exp Mass Screening/
11 Exp cohort studies/ or exp cross-sectional studies/
12 Exp “review”/
13 Mass screen$.tw.
14 Review.ti.
15 1 or 2 or 3
16 4 or 5 or 6 or 7
17 8 or 9 or 10 or 11 or 12 or 13 or 14
18 15 and 16 and 17
19 Limit 18 to (English language and humans)

How this fits in

Chronic kidney disease (CKD) has now been recognised as a major healthcare challenge. The natural history of advanced stages of CKD have been widely reported but less is known about the stage 3 CKD. Stage 3 CKD is the first stage that is identifiable from a blood test alone and accounts for the majority of people on primary care CKD registers. This systematic literature review studied the natural history of stage 3 CKD. It found that mortality was consistently higher and cardiovascular disease was common compared to those without CKD, particularly for those with stage 3B CKD. Risk of progression to ESRD and dialysis was a substantially less frequent outcome.

Inclusion/exclusion criteria

Systematic review, meta-analysis, or follow-up study (prospective or retrospective) of people with CKD that included adults (≥18 years) with stage-3 CKD (GFR 30–59 mL/min/1.73 m2) were considered eligible. Studies were restricted to non-trial study designs. Where a study also included participants in other stages of CKD, it was required that outcome data were presented separately for stage 3. Studies were required to have a minimum of 2 years’ follow-up. Studies with fewer than 100 subjects were excluded. Studies of single specific renal diagnoses or those including only pregnant participants were also excluded.

The primary outcome of interest was all-cause mortality. Secondary outcomes included: cardiovascular morbidity and mortality, and renal outcomes (CKD progression, ESRD or RRT). CKD progression was measured by rate of decline of estimated glomerular filtration rate (eGFR) or creatinine clearance, rise in serum creatinine, or transition through progressive stages of CKD.

Study identification

Two authors independently screened all titles and abstracts to identify potentially relevant studies. Full articles were retrieved in cases of disagreement. All the full articles were assessed against the inclusion and exclusion criteria by two authors. All disagreements were resolved by discussion and there was no need to seek the opinion of a third reviewer. Only those studies presenting relevant outcomes by stage-3 CKD were retained for data extraction and quality assessment.

Data extraction and quality assessment

One author extracted data and assessed the quality of each study using a specifically designed and piloted data-extraction form. A second researcher checked the extracted data for accuracy and disagreements were resolved by a third reviewer. Quality was assessed as described in Table 3. Studies were not excluded based on quality.

Table 3

Quality and judgement criteria.

CriteriaDetails
1. Sample selection Representativeness of the cohort for that community
Study population adequately defined
Information recorded prospectively
Ascertainment of sample described
Assessment of outcome described
2. Follow-up Losses to follow-up less than 10%
Reason for loss to follow-up given
Characteristics of patients lost to follow-up described
3. Other biases Design-specific sources of bias mentioned
Design-specific bias corrected
4. Chronicity CKD defined to be chronic (≥3 months)
5. Measurement of renal impairment Differences in assays over time or between laboratories accounted for
Quality judgement
 Excellent Meeting all criteria (1–5) listed above
 Good Meeting any three or four criteria out of the five criteria listed
 Moderate Meeting any two criteria out of the five criteria listed
 Poor Meeting less than two criteria of the five criteria listed

Quality assessment included generic quality criteria adapted from various methodological quality assessment tools,22–26 and CKD-specific quality criteria adapted from a systematic review of the prevalence of CKD.7 Generic quality issues included sample selection, follow-up, and bias. Specific quality criteria considered the definition of chronicity of CKD and the standardisation of the measure of renal function impairment. It was necessary to establish chronicity in order to exclude acute renal impairment and testing errors and, thus, reduce classification bias. Good-quality studies should use reliable, validated and less-biased assay techniques (modern compensated assays, enzymic assays, assays traceable to gold standard isotope dilution mass spectrometry) to minimise measurement bias.

Synthesis of results

The results were tabulated, grouped by study type, and reported narratively. Relative risk estimates (hazard ratios [HRs] and standardised mortality ratios) were converted to natural logs (ln), and standard deviations estimated to allow graphical presentation using Review Manager software (Version 5). Due to the variability in the reporting of outcomes, data were not pooled in a meta-analysis.

RESULTS

Study selection

Out of 3453 references identified and screened, 118 full papers were retrieved; 17 papers from 13 studies met the inclusion criteria and were critically appraised (Figure 1). Hallan included three papers,27–29 Keith included two papers,30,31 and Eriksen included two papers.32,33 The first study in each is the primary reference and has been quoted throughout. No systematic reviews of the natural history of stage-3 CKD were identified.

Summary of study selection.

Study characteristics

A summary of the characteristics of the included studies is presented in Table 4. There were two methodological groups of studies:

Table 4

Characteristics of included studies

Participants, nMean age of participants, yearsMale participants (%)StudyCohort ascertainmentMinimum follow-up, yearsAllStage 3 CKD (% of total)AllStage 3 CKDAllStage 3 CKDstage 3 CKD only (%)
Clinical population-based cohort-
Chiu et al34 Taiwan, 2008 Referrals to nephrology outpatient clinic 3 433 184(42.5) 65.6 65.7 61.7 74.5 HBP: 6.0 CVD: 27.2 P: 70.6 DM: 30.4
Djamali et al35 US, 2003 Hospital inpatients and outpatients with creatinine >1.3 mg/dL 16 1762 403 (46.0) 54 56 60 54 DM:43
Eriksen and Ingebretsen32 Norway, 2006 Additional publication33 Hospital laboratory database 10 3047 3047(100) 75a 75 30 30 NR
Go et al36 US, 2004 Hospital laboratory database and renal registry 4 1 120 295 3: 187 701 (16.8) 3A: 153 426(13.7) 3B: 34 275 (3.0) 52.2 3A: 65.4 3B: 71.2 45.4 3A: 39.3 3B: 38.4 DM 3A: 12.3 3B: 19.6 CVD3A: 13.2 3B: 20.6 P 3A:8.9 3B: 17.7
Hemmelgarn et al37 Canada, 2006 Regional laboratory database Median 2 (IQR 1.9-2.2) 10 184 3 191 (31.0) range: 75-78 77.8 45.1-37.5 37.5 DM: 19.8
Keith et al30 US, 2004 Additional publication31 Health insurance claims database 5.5 27 998 1 741 (6.2) range: 61-74 71.6 NR 37.8 bDM:15.8 bCVD: 13.1 bHBP: 37.4
Khatami et al38 UK, 2007 Hospital database 4 8160 520 (6.4) Male: 63.5a Female: 67a NR 58.7 NR bDM: 1.3 bCVD: 0.4
O'Hare et al39 US, 2006 Veterans' health Mean 3.17 insurance database (SD 0.62) (128 centres) and National ESRD registry 2 583 911 476 337 (18.4) 63.6 NR 95 NR bDM: 10-36 bCVD: 6-58
Orlando et al,40 US, 2007 Veterans' health insurance (single centre) Approx. 5 (mean 3.5) 1553 416(26.8) 70 NR 100 100 bDM: 52 bHBP: 92 bP: 89
General population-based cohort
Brantsma et al4 the Netherlands, 2008 Health screening: sample enriched for those with albuminuria Median 7.5 (IQR: 6.9-7.8) 8495 491 (31.0) 49.2 63.2 50 53.4 DM: 5.9 HBP: 46.3
Hallan et al27 Norway, 2006 Additional publications28,29 Health screening 10.3 65 604 3: 2973 (4.5) 3A: 2389 (3.6) 3B: 548 (0.8) 49 NR 46.8 NRb DM:3 bHBP: 11.1 bCVD: 7.9
Imai et al42 Japan, 2008 Health screening 10 120 727 3: 25 715(21.4) range 40-79 NR 32.7 NR bHBP: 13.9 bP:1.7
Wen et al43 Taiwan, 2008 Health screening 13 462 293 3: 25 609 (5.5) 3A: 22 597 (4.9) 3B: 3 012(0.7) 41.8 61.9 49.8 53.4 DM: 14.5 HBP: 56.6 P: 20.4

  • Clinical populations (n = nine studies): studies based on participants recruited from a clinical population (those from clinical record databases, laboratories, primary care, or clinical settings).31,32,34–40

  • General populations (n = four studies): studies that were based on participants recruited from a general population (representing people in the community and identified through screening programmes).27,41–43

All but one study,32 reported findings for other CKD stages. The results of the participants with stage-3 CKD have been focused on only.

A total of 728 328 people with stage-3 CKD were included; they accounted for between 4.5%27 and 100%32 of study cohorts. Follow-up varied from 2 years to 16 years. Most of the studies used the Modification of Diet in Renal Disease equation for GFR estimation, but one used the Cockroft and Gault equation.35

Most studies (five) were from the US, with two each from Norway and Taiwan, and one each from the UK, the Netherlands, Canada, and Japan.

Quality of included studies

The quality assessment of included studies is shown in Table 5. None of the studies fulfilled all the quality criteria, however most (nine) were rated as ‘good’ quality; only one of the studies35 was graded as ‘poor’. Six studies established the chronicity of reduced eGFR.

Table 5

Quality assessment of included studies.

Study reference numberQuality criteria41343532362737423038394043
Sample selection
Representative of the community Y Y U Y Y Y Y Y Y U Y Y Y
Study population adequately defined Y Y Y Y Y Y Y Y Y U Y Y Y
Information recorded prospectively Y Y Y Y Y Y Y Y Y Y Y Y Y
Ascertainment of sample described Y Y N Y Y Y Y Y Y Y Y Y Y
Assessment of outcome described Y Y N Y Y Y Y Y Y Y Y Y Y
Follow-up
Loss to follow-up <10% N Y N C N C C C C C U Y C
Reason for loss to follow-up given N N Y n/a Y n/a n/a n/a n/a n/a N n/a
Characteristics of patient loss to follow-up described Y N N n/a Y n/a n/a n/a n/a n/a N n/a
Other biases
Design-specific sources of bias mentioned Y Y Y N N Y Y Y Y N Y Y Y
Design-specific bias corrected Y Y N Y N Y Y Y Y N Y Y Y
Chronicity
CKD defined to be chronic (≥3 months) N Y Y Y Y N N N Y U N Y N
Measurement of renal impairment
Difference in assays over time or between labs accounted for N N N U Y Y Y Y U Y N N Y
Overall quality M G P G G G G G G M M G G

Evidence of mortality

Studies reported two types of mortality results for stage-3 CKD:

  • the rate of mortality (number of deaths in a group per unit of time); and

  • the risk of mortality (number of deaths compared with another group).

Among the nine studies reporting all-cause mortality, only one was a general population-based cohort;43 the other eight included clinical populations.30,32,34–37,39,40 Two studies reported CVD morbidity36,41 and three CVD mortality.27,34,43 Detailed results of all-cause mortality, and CVD morbidity and mortality are given in Table 6 and Figure 2.

Table 6

Summary of all-cause mortality, and CVD morbidity and mortality in stage-3 CKD

StudyMeasuresAll-cause mortalityCVD morbidity and mortalityComments
Clinical population-based cohort
Chiu et al34 CVD deaths
n/N: 11/184 3/184
Rates: 2.1 deaths/100py
6% at 3 years 2% at 3 years
Djamali et al35 n/N: 85/403 (21%) NR
Rates: 21% at 12.6 years NR Adjusted for age and sex
Eriksen and n/N: 959/3047 (31.5%) NR
Ingebretsen32 Rates: 32% at 5 years (95% CI = 30 to 34)
51% at 10 years (95% CI = 48 to 55) NR
Go et al36 CVD eventsa
n/N: Stage 3: 19371/187701 (10.3%) Stage 3: 53270/187701 (28.4%)
Stage 3A: 11569/153426 (7.5%) Stage 3A: 34690/153426 (22.6%)
Stage 3B: 7802/34275 (22.8%) Stage 3B: 18580/34275 (54.2%)
Rates: Stage 3A: 1.1 deaths/100pyb Stage 3A: 3.7/100pyc Compared with those with eGFR ≥60:
Stage 3B: 4.8 deaths/100pyb Stage 3B: 11.3/100pyc
Hemmelgarn et al37 n/N : Stage 3B: 192/3191(6.0%) NR Proportions not reported for stage 3 or 3A
Rates: Not calculabled NR
Keith et al30 n/N: 423/1741 NR
Rates: 24% at 5 years NR
O’Hare39 n/N : NR NR
Rates: Stratified by age group NR
Orlando et al40 n/N: 205/416 NR
Rates: 49% at ∼5 yearse NR
General population-based cohort
Brantsma et al41 CVD events
n/N: NR NR
Rates: NR 2.1/100py Compared with those without
CKD = 0.7/100py
Hallan et al27 CVD deaths
n/N: NR Stage 3: 641/2973 (21.6%)
Stage 3A: 456/2389 (19.1%)
Stage 3B: 185/548 (33.8%)
Rates: NR Stage 3A: 3.5/100py Compared with eGFR ≥60 = 0.4/100py
Stage 3B: 7.4/100py
Wen et al43 CVD deaths
n/N: Stage 3: 3856/25609 (15.1%) Stage 3: 1032/25609 (4.0%)
Stage 3A: 2975/22597 (13.2%) Stage 3A: 778/22597 (3.4%)
Stage 3B: 881/3012 (29.2%) Stage 3B: 254/3012 (8.4%)
Rates: Stage 3: 15% at 13 years Stage 3: 4% at 13 years
Stage 3A: 14% at 13 years Stage 3A: 3% at 13 years
Stage 3B: 29% at 13 years Stage 3B: 8% at 13 years

Relative risk of all-cause mortality, cardiovascular disease mortality, and cardiovascular disease events.

Rates of all-cause mortality, and CVD morbidity and mortality. In the six studies reporting mortality rates,30,32,34–36,39 estimates varied substantially but, where reported, mortality was consistently higher in those who had stage-3 CKD compared with those who did not have CKD. Chiu et al 34 reported the lowest cumulative mortality rate of 6% during 3 years’ follow-up (2.1 per 100 person-years). The highest was reported by Eriksen and Ingebretsen32 with a mortality rate of 32% at 5 years and 51% at 10 years. The mortality rate was substantially higher in stage 3B (4.8 deaths per 100 person-years) compared with stage 3A (1.1 deaths per 100 person-years).36 Stratified annual mortality rates increased with age and eGFR. O’Hare et al 39 reported that the mortality rate in the youngest group of patients (aged 18–44 years) with eGFR 50–59 mL/min/1.73 m2 was as low as 0.8% per year but increased to 14.7% in patients (85–100 years old) with eGFR 30–39 mL/min/1.73 m2.

CVD mortality and events varied, but again was consistently higher in those who had stage-3 CKD as compared to those with no CKD. In a clinical population study, 2% at 3 years were reported to have CVD deaths.34 In general population studies, CVD death rates varied from 4% at 13 years43 to 21% at 10 years.27 CVD mortality rates were higher in stage 3B (7.4 per 100 person-years,27 8% at 13 years43) as compared to stage 3A (3.5 per 100 person-years,27 3% at 13 years43).

CVD event rates also varied from 2.1 per 100 person-years41 to 11.3 per 100 person-years.36 CVD event rates more than trebled from 3.7 per 100 person-years at stage 3A to 11.3 per 100 person-years at stage 3B.36

Risk of all-cause mortality, and CVD morbidity and mortality versus no CKD. Four studies reported the relative risk of mortality for stage-3 CKD as compared with those without CKD.32,36,39,43 A small increase in the risk of mortality (HR 1.2–1.8), after adjustment for differences between the comparison groups in age, sex, and comorbidities, was observed for those people with stage-3 CKD compared with those with eGFR ≥60 mL/min/1.73 m2(36) and eGFR 60–89mL/min/1.73m2 without proteinuria.43 Eriksen and Ingebretsen32 reported an increase in risk of all-cause mortality with an HR of 1.3 (95% CI = 1.1 to 1.4) for each 10 mL/min/1.73 m2 decrease in eGFR. Go et al 36 and Wen et al 43 reported that the relative risk of mortality for stage 3B was almost double that of stage 3A (Figure 2).

O’Hare et al 39 estimated the relative risk of mortality stratified by age and level of renal function across stage 3 (eGFR only reported by following categories: 50–59, 40–49 and 30–39 mL/min/1.73 m2), as compared with eGFR ≥60 mL/min/1.73 m2. For those with eGFR 50–59 mL/min/1.73 m2, older age groups (65–74 years) were found to be at no increased risk of all-cause mortality (HR 1.02, 95% CI = 1.0 to 1.1), whereas in younger patients (aged 18–44 years) the HR was 1.6 (95% CI = 1.3 to 1.9). For those with a lower level of renal function (eGFR 40–49 and 30–39 mL/min/1.73 m2), associated relative risk decreased with increasing age. For example, risk of all-cause mortality for those with eGFR 40–49 mL/min/1.73 m2 decreased from HR 1.9 (95% CI = 1.4 to 2.7 in those aged 18–44 years) to HR 1.4 (95% CI = 1.3 to 1.4 in those aged 65–74 years). Similarly, for those with eGFR 30–39 mL/min/1.73 m2, risk decreased from HR 3.6 (95% CI = 2.5 to 5.1 in those aged 18–44 years) to HR 1.8 (95% CI = 1.8 to 1.9 in those aged 65–74 years).

Two studies reported risk of CVD events,36,41 while only one43 reported risk of CVD mortality. The risk of CVD events was increased in stage-3 CKD, as compared with no CKD (stage-3 HR 1.3 [95% CI = 1.0 to 1.7]41 and stage-3A HR 1.4 [95% CI = 1.4 to 1.5]).36 Stage 3B had a 60% greater risk of CVD events than stage 3A.36 Wen et al 43 reported an adjusted HR of 1.7 (95% CI = 1.5 to 2.0) for CVD deaths for those with stage-3A CKD (as compared with those with eGFR 60–89 mL/min/1.73 m2 without proteinurea), again with a higher risk in those with stage 3B (HR 3.3; 95% CI = 2.7 to 4.1)43 (Figure 2).

Evidence of renal outcomes

Renal outcomes were reported by eight studies and included ESRD, RRT, and CKD progression (Table 7).

Table 7

Summary of renal outcomes in stage-3 CKD

StudyMeasuresESRD or RRTCKD progressionComments
Clinical population-based study
Chiu et al34 ESRD ESRD defined as initiation of RRT
n/N: 7/184 (3.8%) NR
Rates: 1.4/100py Mean GFR decline:
4% at 3 years 2.2 (SE 0.3) mL/min/1.73 m2/year
Djamali et al35 n/N: NR NR
Rates: NR Mean CrCl decline: Progression defined as mean rate of CrCl
5.4 (SD 7.4) mL/min/year decline in mL/min/year
Eriksen and Ingebretsen32 ESRD ESRD defined as stage 5 CKD or initiation of RRT
n/N: 62/3047 (2.0%) Proportion with eGFR decline
>0 mL/min/1.73 m2/year: 73%
>5 mL/min/1.73 m2/year: 6%
Rates: 2% at 5 years mean eGFR decline:
4% at 10 years 1.03 mL/min/1.73 m2/year
Hemmelgarn et al37 n/N: NR NR
Rates: NR eGFR decline Rates adjusted for age, sex, diabetes
(mL/min/1.73 m2/year) mellitus, and comorbidity score; the rates
M: 1.9 (95% CI = 1.5 to 2.3) were for participants without diabetes
F: 1.1 (95% CI = 0.8 to 1.4) mellitus
Keith et al31 RRT
n/N : 23/1741 (1.3%) NR
Rates: 1.3% at 5 years
(transplant: 0.2%; dialysis: 1.1%) NR
Khatami et al38 n/N : NR Progression to stage 4/5: 22/520 Approximate proportions reported for
Rates: NR Progression to stage 4/5: 4% at regression and no progression
4 years
Regression to stage 2: ∼20%
at 4 years
No progression: ∼76% at 4 years
Orlando et al40 n/N: NR 70/416 CKD progression defined as progression to next stage
Rates: NR 17% at ∼5 years
General population-based study
Hallan et al27 ESRD
Hallan et al29 n/N: Stage 3: 16/2973 (0.5%)
Stage 3A: 9/2389 (0.3%)
Stage 3B: 7/548 (1.3%) NR
Rates: Stage 3A: 0.04/100py
Stage 3B: 0.2/100py NR
Imai et al42 n/N : NR NR
Rates: NR Annual progression rate stratified by age, sex and baseline eGFR

End-stage renal disease or renal replacement therapy. Four studies reported rates of ESRD or RRT for specified time periods.27,30,32,34 Cumulative incidence of renal failure at 5 years was 1.3–2% and 4% at 10 years for those with stage-3 CKD.30,32 Chiu et al,34 studying patients referred to a nephrologist, reported an ESRD (defined as initiation of RRT) rate of 1.4 per 100 person-years. Hallan et al,27 in their general population study, reported a lower rate of ESRD for stage-3A CKD (0.04 per 100 person-years) than stage-3B CKD (0.2 per 100 person-years).

One study reported the risk of renal failure32 and one reported the risk of ESRD27 for those with stage-3 CKD, as compared with no CKD. Eriksen and Ingebretsen32 reported an HR of 2.5 (95% CI = 1.9 to 3.3) for each eGFR decrease of 10 mL/min/1.73 m2; a risk 5.3 times greater than the general population (standardised for age and sex). Hallan et al 27 estimated that the risk of progression to ESRD was 11.5 (95% CI = 6.6 to 20.2) for those with stage-3A CKD and 52.6 (95% CI = 29.6 to 93.4) for those with stage-3B CKD, as compared with those without CKD (eGFR ≥60 mL/min/1.73 m2).

CKD progression. Rate of progression, as mean GFR or creatinine clearance decline, was reported by four studies32,34,35,42 and ranged from 1.03 to 5.4 mL/min/1.73 m2/year. Hemmelgarn et al 37 reported greater decline in eGFR per year (adjusted for age) for male participants (1.9 mL/min/1.73 m2/year; 95% CI = 1.5 to 2.3) versus females (1.1 mL/min/1.73 m2; 95% CI = 0.8 to 1.4).

Imai et al 42 graphically presented the annual rate of eGFR decline stratified by different age groups (40–49, 50–59, 60–69 and 70–79 years), sex and baseline eGFR (50–59, 40–49 and 30–39 mL/min/1.73 m2). In general, it was observed that the rate of decline increased as the level of kidney function decreased in both males and females and across all age groups (except in males aged 50–59 years). The highest rate of decline (mean 3.3; standard error of mean 0.7 mL/min/1.73 m2/year) was observed in the youngest male group (aged 40–49 years) with an eGFR of 30–39 mL/min/1.73 m2.

Eriksen and Ingebretsen’s study,32 which included only patients with stage-3 CKD, reported that only 6% had a mean eGFR decline greater than 5 mL/min/1.73 m2 and 27% experienced no decline in function. Khatami et al 38 followed people with eGFR <60 mL/min for 4 years and reported that approximately 4% progressed to stage-4 or stage-5 CKD, 20% regressed to stage-2 CKD and 76% were stable. Orlando et al 40 reported that only 17% of those patients at stage 3 progressed to the next stage during at least 5 years follow-up.

DISCUSSION

Summary of evidence

Despite the substantial focus clinically, and at a policy level, on the management of mild to moderate or ‘early’ CKD, this is, to the best of our knowledge, the first systematic review of the natural history of stage-3 CKD.

The absolute rate of death among those with stage-3 CKD varied between studies but was as high as 51% at 10 years and was markedly higher in stage 3B compared with stage 3A. Compared with those with no CKD, mortality was consistently higher after adjustment of age, sex, and comorbidities. However, the increase was small for those with stage-3A disease and greater in stage 3B. As age increased, the additional risk of death attributable to low eGFR decreased. This has two important implications in general practice: in older age groups, a large number of deaths may occur in patients with CKD; however, because risk of death from other causes is also increased, for the individual patient, the additional diagnosis of CKD has little impact on risk of death.

ESRD was a rare outcome (4% after 10 years follow-up, 0.04 per 100 person-years) but was greater in those with stage-3B CKD compared with those with stage-3A CKD. Where a cohort was selected from a nephrology clinic, the ESRD rate was higher than in general population studies (1.4 per 100 person-years), perhaps reflecting the clinical selection of patients at high risk of developing CKD. This could also highlight why extrapolating the experience from nephrology clinics to community practice and to patients identified through opportunistic or population screening may not be appropriate.

Policy-makers have focused on ‘early’ CKD and ‘early’ detection based on a model of progressive renal-function decline.12 From three studies, it was possible to estimate the proportion of people who did not demonstrate evidence of progressive renal-function decline: Eriksen and Ingebretsen32 reported that 27% showed no fall in eGFR during up to 10 years’ follow-up; two further studies reported that ≥80% did not show any worsening of CKD stage after up to 5 years’ follow-up.38,40 In practice, therefore, the number of patients with stage-3 CKD progressing to ESRD is likely to be low.

Looking for other indicators of underlying pathology and markers of kidney damage will be important in helping to identify which patients are at risk of a progressive course. The number of patients with CKD experiencing cardiovascular events and mortality will be much greater; as such, assessing for cardiovascular risk factors should be an important aspect of CKD patient care. As more experience is gained of the natural history of stage-3 CKD in people identified through opportunistic and population screening, it may become possible to identify those who could benefit most from more intensive management and referral to a nephrology specialist.

Strengths and limitations of the study

This review was undertaken systematically, with pre-specified inclusion and exclusion criteria in order to minimise bias when selecting studies for inclusion. Thirteen studies were identified, nine of which were considered to be of good quality, but all had methodological weaknesses. Six studies used validated methods to establish the chronic nature of eGFR impairment. Although having a clear definition of chronic kidney impairment is of clinical importance and is relevant in identifying those at greater risk of progressive disease, it is important to note that population screening studies, relying on the much less specific marker of a single reduced estimated GFR, still reported the increased risks of mortality.

It has not been possible to produce a pooled estimate of the risk of death or renal disease progression for people with stage-3 CKD. There were inconsistencies in the way studies reported their findings which, along with the clinical heterogeneity in the study populations, meant that a pooled estimate would be uninterpretable. However, the risks are influenced by a range of factors — including age, sex, and comorbidities — and varied with geography (a marker for different ethnic groups and healthcare systems). Adjusted analyses suggest that stage-3 CKD is an independent risk factor for increased mortality and renal progression — a risk that increases as eGFR falls and is substantially greater for those with stage-3B disease than those with stage-3A disease.

A decision was made to exclude data from the control arms of randomised controlled trials (RCTs). Although such studies do provide a view of the natural history of the condition, the strict selection of patients to participate in them means that their outcomes are very different and difficult to generalise. For example, Jafar et al 44 reported a meta-analysis of RCTs for ACE inhibitors in non-diabetic renal disease. From pooled RCT data for CKD stages 3–5, they reported a low all-cause mortality (1.2% in a mean follow-up of 2.2 years) and a relatively high progression to ESRD (11.6%); this reflected the selection of trial participants and the difficulty in generalising such findings. In addition, very few of the intervention trials have reported their findings for stage-3 CKD separately.

Conclusion

In the UK, and internationally, there has been a major drive to detect people with ‘early’ CKD. The QOF supports the identification of people with stage-3 CKD in primary care, and management of their blood pressure in particular. The findings of this review highlight that, for patients identified through opportunistic detection methods where testing was undertaken for a variety of clinical indications, all-cause mortality was higher than for those with no CKD and CVD was common. The risk of progression to ESRD and dialysis was substantially less.

CKD registers provide an opportunity for GPs to assess risk of CVD, and optimise care for individuals at high risk of developing CVD. For many, CKD occurs as part of a complex comorbidity cluster, with hypertension, diabetes mellitus, and CVD; as such, care should not be considered in isolation.

Funding

The work reported in this article is part of a project that was funded by the NIHR Health Technology Assessment Programme (06/75/02). The full report has been accepted for publication in Health Technology Assessment Journal (see HTA programme website for further project information). The views and opinions expressed here are those of the authors and do not necessarily reflect those of the Department of Health.

Competing interests

The authors have stated that there are none.

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Articles from The British Journal of General Practice are provided here courtesy of Royal College of General Practitioners

How long can you stay in stage 3 kidney disease life expectancy?

When diagnosed and managed early, stage 3 CKD has a longer life expectancy than more advanced stages of kidney disease. Estimates can vary based on age and lifestyle. One such estimate says that the average life expectancy is 24 years in men who are 40, and 28 in women of the same age group.

Is kidney disease Stage 3 serious?

How serious is Stage 3 CKD? You might think of Stage 3 CKD as a "middle stage" of kidney disease. Your kidneys are damaged, but they still work well enough that you do not need dialysis or a kidney transplant. Kidney disease often cannot be cured in Stage 3, and damage to your kidneys normally is not reversible.

How long does it take to go from Stage 3 to Stage 4 kidney disease?

Stage 3B patients had higher risks of adverse renal and cardiovascular outcomes than stage 3A patients. Conclusions: About half of the patients with stage 3 CKD progressed to stage 4 or 5, as assessed by eGFR, over 10 years.

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