CKD

1. CHRONIC KIDNEY DISEASE: Epidemiology,
Aetiology, Progression of disease,
Complications and Non-Dialytic
Management
General Medicine Update Course, Faculty of Internal Medicine
Prof EI Unuigbe

2. Objectives
• Definition and staging of CKD
• Epidemiology of CKD
• Aetiology and risk factors for CKD
• CKD progression, risk factors and biomarkers
• Complications of CKD
• Non-dialytic or conservative management of CKD with emphasis on
management of hypertension and diabetes mellitus.

3. Definition and Staging of CKD
• Definition of CKD has evolved over the years.
• CKD is kidney damage for ≥3 months with structural or functional
abnormalities of the kidney with or without decreased GFR and
manifested by either pathological abnormalities or markers of kidney
damage, including urinary or blood abnormalities or abnormalities in
imaging studies
• Or GFR <60mL/min/1.73m2 for 3 months or more
• CKD was classified into stages using GFR and an action plan was
outlined for each stage.
• The above definition was updated in 2012

4. CKD STAGING
Stage Term/Description GFR
(mL/min/1.73m2
Action
1 Kidney damage with normal
or increased GFR
≥90 Diagnosis & treatment,
Treatment of comorbid
conditions,
Slowing progression,
CVD risk reduction
2 Kidney damage with mild
decrease in GFR
60 - 89 Estimating progression
3 Moderate decrease in GFR 30 – 59 Evaluating & treating
complications
4 Severe decrease in GFR 15 – 29 Preparation for kidney
replacement therapy
5 Kidney failure <15 or RRT Replacement therapy if
uraemia present

5. Revised definition of CKD
• CKD defined as abnormalities of kidney structure or function, present for >
3 months, with implications for health
• This definition requires one of two criteria documented or inferred for >3
months (either GFR <60ml/min/1.73m2 or markers of kidney damage such
as albuminuria)
• “Implication for health” added to stress the fact that some abnormalities of
kidney structure or function exist with no health implication for the
individual
• Stage G3 subdivided to G3a (GFR 45-59) & G3b (30-44) because both
subgroups have different outcomes & risk profiles
• In the revised 2012 definition, CKD is classified based on cause, GFR
category, and albuminuria category (CGA) rather than just GFR alone.

6. CKD STAGING
Stage Term/Description GFR
(mL/min/1.73m2
1 Kidney damage with normal
or increased GFR
≥90
2 Kidney damage with mild
decrease in GFR
60 - 89
3a Mild to moderate decrease
in GFR
45 – 59
3b Moderate to mild decrease
in GFR
30 – 44
4 Severe decrease in GFR 15 – 29
5 Kidney failure <15 or RRT

7. Markers of kidney damage
Can be one or more of the following:
• Albuminuria (AER ≥30mg/24 hours, ACR ≥30mg/mmol, ≥30mg/g)
• Urine sediment abnormalities
• Electrolytes & other abnormalities due to tubular disorders
• Abnormalities detected by histology
• Structural abnormalities detected by imaging
• History of kidney transplantation

8. CKD STAGING
KI Supplements (2013) 3, 5-14

9. Epidemiology
• CKD is a global public health problem, with rising incidence & prevalence
• Poor outcomes and cost of management is enormous to both families and
governments.
• According to the Global Burden of Disease Study CKD ranked 27th in 1990 and 18th
in 2010 on the list of causes of global death.
• Prevalence between 8% and 16% worldwide.
• Age-standardised prevalence rate of CKD worldwide in adults aged 20 years and
above is 10.4% for men and 11.8% for women.
• Prevalence higher in low and middle-income countries compared to high-income
countries.
• Prevalence is higher in women but men have a more rapid progression of CKD to
ESRD compared to women; and generally for both men and women, prevalence
of CKD increases with age in high, low and middle-income countries.

10. Annual prevalence rates of ESRD in different countries
Lancet Global Kidney Disease May 2013, 27-39. www.thelancet.com

11. NIGERIAN DATA
❖CKD prevalent in Nigeria
❖Accurate prevalence data lacking mainly because of absence of a
national registry or national data except for a few community-based
reports
❖Hospital prevalence studies report ESRD accounting for 6% - !2% of
medical admissions
❖Prevalence estimated to range between 2.5% and 27% depending on
which region of the country the report is from
❖CKD affects young people aged between 26 – 45 years
❖Patients present late in ESRD

12. 11.4%
27.2%
10.4%
16.0%
0%
5%
10%
15%
20%
25%
30%
Ulasi et al, Enugu Okoye et al, Benin City Afolabi et al, Ilesha Oluyonbo et al, Ife
Prevalence of CKD in Nigeria

13. AETIOLOGY
A. Congenital & inherited
▪ ADPKD
▪ Alport’s syndrome
▪ Fabry’s disease
▪ Tuberose sclerosis
▪ Oxalosis
▪ Cystinosis
B. Vascular diseases
▪ Hypertension → hypertensive nephrosclerosis
▪ Renovascular dis (renal artery stenosis)
▪ Vasculitis (small & medium sized vessel vasculitis)
▪ Renal vein thrombosis

14. Aetiology
C. Glomerular diseases
▪ Primary
Minimal change disease FSGS
IgA nephropathy Membranous nephropathy
Membrano-proliferative GN Rapidly progressive GN
Complement-related diseases (e.g. atypical HUS, dense deposit
disease)
▪ Secondary glomerular diseases Neoplasia
Diabetes mellitus Amyloidosis
Systemic lupus erythematosus Thrombotic thrombocytopenic purpura
Connective tissue diseases Henoch-Schonlein purpura
Granulomatosis with polyangitis (Wegener’s granulomatosis) Endocarditis
Hepatitis B & C, HIV infection

15. Aetiology contd
D. Tubulo-interstitial diseases
▪ Chronic pyelonephritis
▪ Reflux nephropathy (vesico-ureteric reflux)
▪ Analgesic nephropathy
▪ Tuberculosis
▪ Multiple myeloma
▪ Toxic nephropathy (herbs including aloe vera)
E. Obstructive uropathy
▪ Calculi
▪ Prostatic dis (eg BPH)
▪ Pelvic tumors
▪ Retroperitoneal fibrosis
▪ Schistosomiasis
F. Unknown aetiology

16. Aetiology
Common causes of CKD in Nigeria
1. Hypertension
2. Chronic GN
3. Diabetes mellitus
4. HIV infection
5. Toxic nephropathy
Covid-19 infection
In the US common causes
1. Diabetes mellitus
2. Hypertension
3. Chronic GN
4. Cystic disease
Covid-19 infection

17. Aetiology
The list of causes is not exclusive
Important to determine the aetiology of CKD as this has implications
for prognosis & treatment
e.g. stopping culprit drugs in patients with analgesic nephropathy,
treatment of tuberculosis
ADPKD may progress to ESKD faster than other causes, need for
specific treatments to slow down decline of GFR, evaluation for
extra-renal manifestations & follow-up of relatives of patient

18. Aetiology
Apart from causes listed earlier, there are factors that contribute to
increased risk of CKD, affect initiation and progression of CKD
▪ Family history of CKD Dyslipidaemia
▪ Gender Smoking
▪ Ethnicity/Race/Genetics Nephrotoxins
▪ Age Acute kidney injury
▪ Low birth weight Diabetes mellitus
▪ Obesity Hypertension
▪ Socio-economic status

19. Risk factors for CKD
▪ Family history of CKD
▪ Gender
▪ Ethnicity/Genetics
▪ Age
▪ Low birth weight
▪ Dyslipidaemia/Obesity
▪ Socio-economic status
▪ Smoking
▪ Nephrotoxins
▪ Acute kidney injury
▪ Diabetes mellitus
▪ Hypertension
▪ Sickle cell disease
▪ Newly defined risk factors

20. Progression of CKD
• CKD progression defined as a decline in GFR category e.g. a drop in eGFR is
defined as a drop in GFR category accompanied by a 25% or greater drop in eGFR
from baseline.
• CKD progression is associated with progressive glomerulosclerosis irrespective of
underlying nephropathy
• Monitor progression with proteinuria & GFR; monitoring progression allows for
decision making;
▪ CKD progression is said to be rapid if there is a sustained decline in eGFR of more
than 5ml/min/1.73m2/year.
▪ Assess GFR and albuminuria at least annually. More frequent assessment in
those at higher risk of progression and/or where measurement of these indices
will impact therapeutic decisions
• Review current management, examine for reversible causes of progression and
consider referral to a specialist when progression is ascertained in CKD patients.

21. CKD Progression
• Most patients in CKD stages 3 – 5 will progress to ESRD
• In some there is often a straight line relationship between the
reciprocal of serum creatinine (1/sCr) and time
• Some do not follow this linear pattern & may have breakpoints in
their progression slopes when there is acceleration or slowing down
of expected rate of progression
• These breakpoints can be due to events such as infections,
uncontrolled BP, dehydration, exposure to nephrotoxins &
radiocontrast agents

22. CKD Progression
Rate of progression is dependent on the aetiology of CKD, the
individual
• Diabetic nephropathy progresses very fast compared to other
nephropathies (about 10ml/min/year)
• In non-diabetic nephropathy, rate of progression is 2.5 times faster in
patients with CGN than in those with chronic interstitial nephritis &
1.5 times faster than in those with hypertensive nephrosclerosis
• Good control of hypertension slows rate of progression
• Proteinuria is associated with faster progression
• CKD patients with PKD have a faster rate of progression

23. CKD Progression
Monitor progression using proteinuria & GFR trends
• Use ACR to assess proteinuria trend; do every 2-3 months & 4-6
months for patients with nephrotic & non-nephrotic range
proteinuria respectively
• For GFR trends do serial serum creatinine measurements for GFR
estimation.

24. CKD Progression Markers & Factors
▪ Non-modifiable risk factors
1. Age
2. Gender
3. Race
4. Genetics (apolipoprotein L1 (APOL !)
▪ Modifiable risk markers & factors
1. Hypertension
2. Proteinuria
3. Diabetes mellitus
4. Dyslipidaemia
5. Obesity
6. Hyperuricaemia
7. Smoking
8. Alcohol & recreational drugs
9. NSAIDs

25. Biomarkers for CKD Progression
▪ Traditional biomarkers
Creatinine, cystatin C, proteinuria.
▪ Novel biomarkers
Fibroblast growth factor-23 (FGF-23)
Neutrophil gelatinase-associated lipocalin (NGAL)
Kidney injury molecule-1 (KIM-1)
Soluble urokinase-type plasminogen activator receptor (suPAR)
Uromodulin (UMOD)

26. COMPLICATIONS OF CKD
❖Ureamia
❖MaLnutrition
❖Fluid, electrolyte & acid-base disorders (salt & water retention, hyparkalaemia)
❖Mineral bone disease (osteomalacia, osteoporosis, osteosclerosis, adynamic bone dis).
Hypocalcaemia, hyperphosphataemia and hyperparathyroidism present
❖Endocrine disorders ( ↓ erythropoietin, ↓ 1,25 DHCC, ↑ renin, ↓ insulin excretion)
❖Aneamia (usually normochromic normocytic)
❖Metabolic disorders ( gout, lipid metabolism abnormalities)
❖CVS (MI, cardiac failure, hypertension, pericarditis)
❖CNS (PN, autonomic neuropathy, restless leg syndrome, encephalopathy)
❖Decreased immunity
❖Anxiety & depression

27. NON-DIALYTIC MANAGEMENT OF CKD

28. Investigations
A. Urine
1. Urinalysis - haematuria in GN
- proteinuria in glomerular dis
- glycosuria
- SG fixed at 1.010
2. Urine microscopy - granular & red cell casts
3. 24 hours urine for creatinine clearance, protein excretion; spot
urine sample for ACR

29. Investigations
B. Blood
➢ FBC, ESR
➢ E/U. creatinine. Serum creatinine does not begin to rise until 50% of renal function is lost.
Once raised can be used to follow up progression of dis. Also use SCr to calculate or estimate
GFR using the Cockcroft-Gault formula, the MDRD formula, CKD-EPI formula.
➢ Ca ↓, Po4 ↑
➢ Uric acid ↑
➢ Lipid profile
➢ Serum albumin levels (hypoalbuminaemia due to malnutrition, urinary protein loss, or chronic
inflammation)
➢ Viral studies (hepatitis B, C, HIV)
➢ Other ancillary tests depending on aetiology of CKD (serum & urine electrophoresis in patients
with multiple myeloma, antinuclear antibodies, double stranded DNA in SLE etc)

30. Investigations
C. Radiological
➢ Renal Scan → bilaterally shrunken kidneys, echogenic kidneys with loss of cortico-
medullary differentiation, hydronephrosis in those with obstructive uropathy
➢ Plain abdominal X-Ray → stones
➢ CT scan for ∆ of retroperitoneal fibrosis & some causes of urinary obstruction e.g.
stones
➢ MRI for renovascular dis e.g. renal vein thrombosis
➢ IVU but seldom necessary becos serum urea may be ↑ at time of presentation
D. ECG
E. ECHO
F. Renal biopsy: may enable you pick up treatable causes of CKD

31. MANAGEMENT OF CKD
❖ Identify & treat underlying cause of CKD (e.g. withdraw drugs in analgesic nephropathy, treat renal Tb). This helps to delay
or halt progression of CKD
❖ Search for & tackle reversible factors that can worsen renal function & precipitate ureamic state (hypertension, UTI,
nephrotoxic drugs, hypotension, hypovolaemia)
❖ Dietary management
❖ Control serum calcium & phosphate & suppress PTH production
❖ Control hypertension.
❖ Treatment of anaemia
❖ Judicious use of drugs
❖ Lipid lowering drugs eg statins
❖ Cessation of smoking: smoking besides increasing risk of CVS events, is also a factor for development of ESRD in men with
kidney dis
❖ RRT for those in ESRD (dialysis, transplantation). Begin preparation for RRT when patient has reached stage 4 CKD

32. Overview of Management of CKD
• Reduce risk of cardiovascular disease
• Manage hypertension
• Management of diabetes mellitus
• Management of anaemia
• Management of electrolytes & mineral bone disorders
• Counsel patients to avoid use of nephrotoxins such as NSAIDs, herbal medications
etc
• Adjustments of drug dosing
• Dietary management
• When CKD diagnosis is established, KDIDO recommends monitoring of eGFR &
albuminuria at least once annually, twice a year for those at high risk & thrice a
year for patients on very high risk

33. Management of Hypertension
Hypertension present > 80% of patients with CKD; its treatment very important
• Contributes to progression to ESRD, cardiovascular events such as MI, strokes & cardiovascular
deaths
• Hypertension co-existing with proteinuria increases risk of disease progression & CVD events
• Recommended blood pressure goal is systolic BP <130mmHg, diastolic BP <80mmHg
• Non-pharmacologic and pharmacologic approaches
• Treatment goals are
1. Lower blood pressure
2.. Block the renin-angiotensin-aldosterone system using an ACE inhibitor or ARB
3. Mineralocorticoid-receptor antagonists (MRAs). Aldosterone has been linked to
progression of hypertension & MRAs used with ACEIs or ARBs reduces albuminuria;
hyperkalaemia a problem with its use.

34. Management of Hypertension
Non-pharmacologic approach
• Reduce salt intake to <2g sodium/day (or <90mmol of sodium/day or
<5g of sodium chloride/day)
• Cessation of smoking
• Moderate-intensity physical activity (e.g. brisk walking, swimming,
aerobics) for at least 150 minutes/week (30 minutes 5 times/week)
• Weight loss for the overweight, achieve a BMI of 20-25kg/m2
• Moderate alcohol consumption
• Diets rich in fruits, high fibre vegetables, low fat dairy products

35. Management of Hypertension
KDIGO recommends
• BP-lowering drugs for both diabetic and non-diabetic adults with CKD &
UAE <30mg/24 hours whose BP is consistently >140mmHg systolic or
>90mmHg diastolic
• BP-lowering drugs for both diabetic & non-diabetic adults with CKD & with
UAE ≥30mg/24 hours whose BP is consistently >130mmHg systolic or
>80mmHg diastolic
• Use ARB Or ACE-I in both diabetic & non-diabetic adults with CKD & UAE
>300mg/24 hours
• Diuretics, beta-blockers or CCBs can be used as add on antihypertensives
• Treat adult kidney transplant recipients with hypertension to a target BP of
<130 systolic & <80 diastolic. Use a dihydropyridine calcium channel
blocker or an ARB as first line drugs

36. Reduce risk of CVD
• Prevalence of CVD is very high in patients with CKD compared with
those without CKD
• CKD associated with higher risk of coronary artery disease, myocardial
infarction, heart failure, atrial fibrillation, CVA/TIA; need to reduce
risk of cardiovascular events
• Low to moderate dose statin regardless of LDL-cholesterol levels
• Cessation of smoking
• KDIGO recommends SBP & DBP of <140 & <90 respectively
36

37. Management of Diabetes Mellitus
KDIGO Guidelines
• Patients with diabetes & CKD should be treated comprehensively to reduce risks
of kidney disease progression & CVD
• In patients with diabetes, hypertension & albuminuria initiate treatment with
ACE-I or ARB
• For patients with diabetes, albuminuria & normal BP, treatment with ARB can be
considered
• Cessation of smoking
• Use HbA1c to monitor glycaemic control in patients with CKD & diabetes; do at
least twice a year
• Individualised HbA1c target ranging from <6.5% to <8.0% in patients with
diabetes & hypertension not treated with dialysis

38. Management of Diabetes Mellitus
• Patients for whom prevention of complications is key goal, a lower HbA1c target
of <6.5% or <7.0% preferable while in those with multiple co-morbidities or
increased burden of hypoglycaemia, a higher target of <7.5% or <8.0% may be
preferable
• Glycaemic management for patients with type 2 DM should include lifestyle
management, first-line treatment with metformin & a sodium-glucose
cotransporter inhibitor (SGLT2i) & additional drug therapy as needed for control
• Most patients withT2D, CKD & a GFR ≥30ml/min/1.73m2 will benefit from
treatment with combination of both metformin & an SGLT2i
• For patients withT2D & CKD who have not achieved individualised glycaemic
control targets despite use of metformin & SGLT2i or who are unable to use these
medications, a glucagon-like peptide-1 receptor antagonist (GLP-1 RA) is
recommended

39. Dietary management
1. Low protein diet (40gms/day) to reduce blood urea, symptoms of
ureamia & slow down progression
2. Restrict Na intake when patient has oedema or hypertension
3. K+ restriction when there is hyperkalaemia, ion exchange resins
4. Dietary control in those with hyperlipidaemia

40. Management of Anaemia
• Diagnose anaemia & initiate evaluation for its cause
• Anaemia of CKD is often normochromic normocytic
• Haemoglobin level is preferable to haematocrit
• Minimum evaluation for anaemia in CKD should include Hb level,WBC &
differential, platelet count, RBCs indices (e.g. MCV, MCHC), absolute
reticulocyte count, iron studies (ferritin, transferrin saturation)
• Screen CKD patients for anaemia at least once a year
• Treat anaemia with erythropoiesis-stimulating agents (ESAs) such as
erythropoietin after correcting iron deficiency if present; blood
transfusion, haematinics where necessary

41. Control serum Calcium and phosphate
1. Calcium supplements
2. Phosphate binders to ↓ Po4 absorption (eg calcium carbonate po)
3. Calcitriol or Vit D analogue like alfacalcidol to correct for
hypocalcaemia
4. Calcimimetic agents to suppress PTH levels & lower Ca x Po4
products in pts with established 2ry hyperparathyroidism.
Cinacalect is a calcium-sensing receptor agonist

42. Emerging strategies in treatment of CKD
• Uric acid lowering therapy
• Bicarbonate therapy. Acidosis implicated in progression of renal
disease
• Endothelin antagonists. Endothelin is a potent vasoconstrictor and
modulates renal blood flow & GFR; these effects contribute to the
pathogenesis & progression of kidney failure
• Vitamin-based therapies such as vitamin D receptor blockers

43. THANK YOU.

44. References
• KDIGO 2012 Clinical Practice Guidelines; KI Supplements 2013: 3: 1 -150
• Lozano R et al, Lancet 2013; 2095 – 128)
• Lancet Global Kidney Disease May 2013, 27-39. www.thelancet.com
• Seminars in Nephrology 2016; 36(4): 273-282
• JAMA 2019; 322(13): 1294-1304
• Medscape July 21, 2021
• Seminars in Nephrology 2016; 36(4): 331-342
• Ann Intern Med 2013;158:825-830
• Kidney Int Suppl 2021; 99(35)
• Kidney Int Suppl 2020; 98(45)