Delaying CLD progression and managing it complications. According to the KDIGO guidelines

1. Delaying CKD
progression and
managing it’s
complications .

2. Functions of the kidney.
1. Excretory functions.
2. Fluid balance.
3. Synthetic functions.

3. 1. Excretory functions.
•Elimination of uremic toxins .
•Maintaining acid-base balance .
•Maintaining potassium balance.

4. 2. Fluid balance
•Urine production and maintaining
euvolemia.
•Blood pressure control.

5. 3. Synthetic functions.
•Erythropoietin production for RBC synthesis.
•Production of active Vit D through 1- alpha
hydroxylase to maintain calcium and phosphate
balance.
•Blood pressure control through synthesis of
renin.

6. Pathophysiology of CKD.
Pathogenic insult to the kidney.
Leading to a reduction in the number of
functional nephrons and glomerular
damage.

7. Glomerular sclerosis.
Increase blood flow through normal
glomeruli.

8. Increased intra- glomerular pressure.
further damage and sclerosis of
remaining glomeruli.
Progression of CKD.

10. Measures to delay progression.
1. Life style measures.
2. Physical activity.
3. Diet.
4. Blood pressure control.
5. Drugs reducing CKD progression.

11. 6. Metabolic acidosis.
7. Hyperkalemia in CKD.
8. Hyperuricaemia in CKD.
9. Prevention of cardiovascular diseases in CKD.
10. Anemia in CKD.

12. 1. Life style measures.
Avoiding tobacco products.
1.KDIGO recommends complete cessation of
tobacco use.
2. This reduces premature mortality from
CVD as well as risk of respiratory diseases and
cancer.
3. Counselling and pharmacological interventions
such as nicotine replacement therapy of nicotine

13. 2. Physical activity.
•Moderate intensity physical activity for a
cumulative duration of at least 150mins per
week, or to a level compatible with their
cardiovascular and physical tolerance.
•For europeans a BMI of less than 25 and
for asians a lower BMI is recommended.

14. 3. Diet.
•Higher consumption of plant based food
compared to animal based foods and a lower
consumption of ultra-processed food is
recommended.
•A whole- food, plant - based diet low in animal
based and ultra processed foods may be
helpful to slow down the progression of
CKD and delay need for dialysis via reduction
of cardio metabolic risk factors.

15. •A plant based diet is rich in anti inflammatory
nutrients, fiber and phytochemical and has
shown to reduce proteinuria and reduce
metabolic acidosis.
•Pro biotic nature of plant based foods may
also support the microbiome and reduce
inflammation and intestinal production of
uremic toxins.
•These diets reduce CKD progression and
mortality.

16. • A protein intake of 0.8g/kg Body weight is
recommended in stage 3 to 5 CKD.
• Protein catabolism leads to the accumulation of
waste products such as urea and other uraemic
toxins.
• High protein intake also contributes to increased
intra glomerular pressure and progressive
glomerulosclerosis.
• Low protein diets are not supported ( 0.4-0.6g/kg).

17. • In a meta analysis of people with CKD without DM, a low
protein diet compared with a normal protein diet in CKD
stage 3 and 4 found little or no difference in the
participants who reached kidney failure.
• But research has shown that in stage 4 and 5 CKD
without DM, very low protein diets (0.3 to 0.4g per kg)
reduce the number of people who reach kidney failure.
• As a very low protein diet increases the risk of essential
amino acid deficiency, addition of supplements of
essential amino acids or precursors of essential amino
acids( keto acid analogues) is recommended.

18. •Keto acid analogues serve as substrates for
protein synthesis without the production of toxic
nitrogenous waste products.
•However most trials for protein restriction were
conducted before RASi and SGLT2i were
implemented.
•So if proceeding with a low protein diet it is
important to consider dietitian follow up and
financial and cultural restraints.

19. •Sodium intake should be less than 2g per
day.
•Reduction in sodium showed to lower BP
and reduce the cardiovascular risks.
•In people with CKD who have salt
wasting kidney disease, malnutrition or
exposed to extremely hot climates this
recommendation doesn’t apply.

20. 5. Drugs reducing CKD progression.
1. RAS inhibitors.
2. SGLT 2 inhibitors.
3. Mineralocorticoid receptor antagonists.
4. GLP1 agonists.

21. 1. RAS inhibitors.
• ACEI or ARB should be started for CKD ( Stage 1 to 4) with
U ACR more than 300mg/g without DM. (1B)
• Should be started in people with CKD ( stage 1 to 4) and
ACR 30- 299 mg /g without DM. ( 2C)
• Should be started in people with CKD and proteinuria of
more than 30mg/g with DM. ( 1B)

22. • A combination of two RASi is not recommended.
• Should be administered at the highest approved dose
tolerated.
• Changes in BP, S. Cr and S.K should be checked with
in 2-4 weeks of initiation or increase in the dose of a
RASi.
• Hyperkalaemia associated with the use of RASi can be
often managed by measures to reduce K levels rather
than decreasing the dose or stopping RASi.

23. •Consider reducing the dose or discontinuing ACEI
or ARB in the setting of symptomatic hypotension,
uncontrolled hyperkalemia or to reduce uremic
symptoms while treating kidney failure when
eGFR< 15.
•Consider starting people with CKD with normal to
mildly increased proteinuria on RASi for specific
indications. ( HTN or HF with reduced EF)
•RASi should not be discontinued in stage 4-5 CKD.

25. 2. SGLT 2 inhibitors.
•Recommend in people with T2DM, CKD and
an eGFR more than 20ml/ min. Once
initiated it can be continued even if the
eGFR<20ml/ min unless it is not tolerated or
RRT is initiated. (1A)
•Should be withheld during periods of
prolonged fasting, surgery or critical illness.

26. •Adults with CKD with eGFR more than 20
with urine ACR more than 200mg/g or
heart failure irrespective of level of
albuminuria should be started.
•SGLT 2 inhibitors reduce risk of kidney
failure, cardiovascular mortality and heart
failure in CKD. They also favourably
reduce BO, Uric acid levels, fluid overload
and risk of hyperkalemia without
increasing the risk of hypoglycaemia.

27. •Recommended with eGFR 20 to 45ml/
min with urine ACR < 200mg/g even in
non diabetics. (2B)
•SGLT 2i initiation or use does not
necessitate alteration of frequency of
CKD monitoring and the reversible
decrease in eGFR on initiation is
generally not an indication to
discontinue treatment.

28. 3.) Mineralocorticoid receptor
antagonists.
•A non steroidal mineralocorticoid
receptor antagonist with proven renal or
cardiovascular benefits is recommended
for adults with T2DM, eGFR> 25ml/min,
normal serum potassium concentration
and albuminuria > 30mg/g despite
maximum tolerated dose of RASi. (2A)

29. • Can be added to a RASi and a SGLT 2 inhibitor for treatment
of T2DM and CKD.
• To mitigate the risk of hyperkalemia, select people with
consistently normal serum potassium and monitor serum
potassium regularly while on treatment.
• A steroidal MRA may be used for treatment of HF,
Hyperaldosteronism or refractory hypertension, but may
cause hyperkalemia or a reversible decline in GFR.
• Finrenone reduced the cardiovascular risk in people with
CKD and T2DM.

31. 4. GLP1 Agonists.
•In adults with T2 DM and CKD who
have not achieved individualized
glycemic targets despite use of
metformin and SGLT 2 inhibitor
treatment, or who are unable to use
those medications should be started on
GLP1 agonists. (1B)

32. •It reduces the weight and risk of CVD in people
with CKD. Also reduces all cause mortality.
•Long acting GLP 1 agonists are prioritize ahead
of insulin in people with T2DM and CKD.
•GLP 1 RAs with proven CVD benefit that do not
require dose adjustment in CKD include
liragultide, semaglutide and dulaglutide.

33. 6) Metabolic acidosis.
•Increases protein catabolism, muscle
wasting, inflammation, impairs cardiac
functions, increases mortality and
reduces eGFR.
•S. HCO3 starts to fall when eGFR<60
with a more rapid fall when eGFR < 30.

34. •In people with CKD, consider use of
pharmacological treatment with or without
dietary intervention to prevent the development
of acidosis.
•Monitor treatment for metabolic acidosis to
ensure it does not result in S HCO3
concentration exceeding the upper limit of
normal and does not adversely affect BP
control, potassium level or fluid status.

35. •Placebo control trials have found no
good evidence that correcting HCO3
levels affect clinical outcomes.
•It is suitable to initiate NaHCO3 when S
HCO3 level is less than 18mmol/L but
no research proven threshold has been
found.
•Plant based diets help to reduce

36. 7. Hyperkalemia in CKD.
•Uncommon when eGFR > 60ml/ min and
increases with lower GFR.
•Risk factors for hyperkalemia includes higher
I ACR, prior DM, Constipation, RASi and
MRA. SGLT 2 inhibitors do not increase the
risk of hyperkalemia.

37. •There is a U shaped relationship
between serum potassium levels
and all cause mortality and is
associated with a poor renal
prognosis.

38. •1st line Mx- Address correctable
factors
•Review non RASi medications. (
NSAIDs, trimethoprim). Assess
dietary potassium intake and
consider appropriate moderation of
dietary potassium intake.

39. •2nd line Mx- consider
appropriate use of diuretics,
optimize HCO3 levels and start
K exchange agents

40. •3rd line Mx- Reduce dose or
discontinue RASi/ MRA. (
Discontinuation is associated with
increased cardiovascular events.
Review and restart RASi or MRA
at a later date if patients condition
allows)

41. Diet
•In stage 1 and 2 of CKD high intake of foods
rich in potassium appears to be protective
against disease progression and improves
cardiac health.
•Limiting the intake of foods rich in
bioavailable K is recommended in people
with stage 3 CKD and above if they have a
history of hyperkalaemia or as a prevention
strategy during disease periods in which
hyperkalemia risk may be a concern.

42. •Highly processed foods, meats, dairy
products, juices and salt substitutes made
with KCL are higher in absorbable
potassium than plant based fresh foods.
•Cooking methods such as soaking foods
for 5 to 10 mins in previously boiled water
can reduce the amount of potassium.

43. Potassium exchange agents.
•For people with CKD and severe
recurrent hyperkalemia (>6) if the
cost vs benefit is higher towards
hyperkalemia prevention, long
term K exchange agents may be
beneficial.

45. Suggested action in moderate and severe
hyperkalemia.
•Sever;
If more than 6.5-Immediate assessment and
ECG monitoring.
•Moderate ;
6 to 6.4- If clinically unwell or AKI assess and
treat in hospital. If unexpected result repeat
within 24hrs.

46. 8. Hyperuricamia in CKD.
•Defined as a uric acid level more than
6.8mg/dL.
•People with CKD and symptomatic
hyperuricameia should be offered uric
acid lowering interventions.

47. •If a CKD stage 3 to 5 patient presents
with a 1st episode of gout, serum uric
acid > 9mg/dL or urolithiasis a uric acid
lowering agent should be offered.
•This is because there is a higher risk of
progression of gout in CKD. If started it
should be given indefinitely.

48. •Xanthine oxidase inhibitors such as allopurinol
and febuxostat are preferred over uricosuric
agents ( Probenacid) as their effect is blunted at
a low GFR.
•In acute gout low dose colchicine or steroids are
preferred over NSAIDs.
•Agents used to lower uric acid levels are not
recommended in people with CKD and
asymptomatic hyperuricaemia.

49. 9. Prevention of cardiovascular disease in CKD.
1.Lipid management.
2.Anti platelets.
3.Invasive vs intensive medical
therapy for coronary artery disease.
4.Atrial fibrillation.

50. 1 Lipid management.
•In adults aged 50y or more with GFR less
than 60, not treated with hemodialysis or
renal transplant, treatment with a statin or
statin/ ezetimibe combination is
recommended. ( 1A)
•In adults aged 50y or more with CKD and
eGFR >60 statin treatment is recommended

51. •In adults aged 18 to 49y with CKD but
not treated with HD or KT, we suggest
statin treatment in people with one or
more of the following (2A):
• - Known coronary artery disease
• - DM
• - Prior ischemic stroke
• - Estimated 10y CV risk> 10%

52. •Large trials have shown the following
once daily intensive statin based
regimens are safe in CKD ( Including
pts on HD)
•Atorvatatin 20mg Rosuvastation 10mg
•Consider a plant based Mediterranean
diet.

53. 2. Anti platelets.
•Oral low dose aspirin is
recommended for 2ry prevention of
cardiovascular disease. (1C)
•Not recommended for primary
prevention.

54. •For those with high GI bleeding
risk, PPIs are effective, safe and
low cost and can be used in CKD. (
Occasionally interstitial nephritis
can occur)
•P2Y12 inhibitors can be used if
intolerant to aspirin or if dual anti
platelets are needed.

55. 3. Invasive vs intensive medical therapy for
coronary artery disease
•In stable stress test confirmed IHD, an initial
conservative approach using intensive
medical therapy is an appropriate alternative
to an initial invasive strategy. (2D)
•Invasive strategy is preferred in severe
angina, Left ventricular failure or left main
stem disease.

56. 4. Atrial fibrillation.
•NOACs are preferred over Vit K antagonists
in AF in people with stage 1 to 4 CKD.
•NOACs reduce the risk of intracranial
bleeding compared with warfarin. They don’t
need monitoring.
•Dose adjustments are needed depending on
eGFR.

57. 10. Anemia in CKD.
•Investigation of anemia
• In patients with CKD and anemia
(regardless of age and CKD stage),
include the following tests in initial of
the anemia (Not Graded)

58. •• Complete blood count (CBC), which
should include Hb concentration, red
cell indices, white blood and differential,
and platelet count
•Absolute reticulocyte count
•Serum ferritin level
•Serum transferrin saturation (TSAT)
•Serum vitamin B12 and folate levels

59. Treatment with iron agents.
• When prescribing iron therapy, balance the
potential benefits of avoiding or minimizing
blood transfusions, ESA therapy, and
anemia-related symptoms against the risks
of harm in individual patients (e.g.,
anaphylactoid and other acute reactions,
unknown long-term risks). (Not Graded)

60. •For adult CKD patients with anemia
not on iron or ESA therapy we suggest
a trial of IV iron (or in CKD ND patients
alternatively a 1-3 month trial of oral
iron therapy) if (2C)
•an increase in Hb concentration
without starting ESA treatment is
desired
•TSAT is ≤30% and ferritin is ≤500

61. •For adult CKD patients on ESA therapy
who are not receiving iron
supplementation, we suggest a trial of IV
iron (or in CKD ND patients alternatively
a 1-3 month trial of oral iron therapy) if
(2C):
•an increase in Hb concentration without
starting ESA treatment is desired**
•TSAT is ≤30% and ferritin is ≤500 ng/ml

62. •For CKD ND patients who require
iron supplementation, select the
route of iron administration based
on the severity of iron deficiency,
availability of venous access,
response to prior oral iron therapy,
side effects v oral or IV iron therapy,
patient compliance, and cost. (Not
Graded)

63. •Guide subsequent iron
administration in CKD patients
based on Hb responses to recent
iron as well as ongoing blood
losses, iron status tests (TSAT and
ferritin), Hb concentration, ESA
response and ESA dose in ESA
treated patients, trends in each
parameter, and the patient's
clinical status (Not Graded)

64. • For all pediatric CKD patients with anemia not on
iron or ESA therapy, we recommend oral iron (or IV
iron in CKD HD patients) administration when TSAT
is r20% and ferritin is r100 ng/ml (r100 lg/l). (1D)
•For all pediatric CKD patients on ESA therapy who
are not receiving iron supplementation, we
recommend oral iron (or IV iron in CKD HD
patients) administration to maintain TSAT 420%
and ferritin 4100 ng/ml (4100 lg/ l). (1D)

65. Iron status evaluation.
• Evaluate iron status (TSAT and ferritin) at least every 3
months during ESA therapy, including the decision to start
or continue iron therapy. (Not Graded)
• Test iron status (TSAT and ferritin) more frequently when
initiating or increasing ESA dose, when there is blood loss,
when monitoring response after a course of IV iron, and in
other circumstances where iron stores may become
depleted. (Not Graded)

66. Cautions regarding iron therapy.
•When the initial dose of IV iron dextran is
administered, we recommend (1B) and when the
initial dose of IV non- dextran iron is administered,
we suggest (2C) that patients be monitored for 60
minutes after the infusion, and that resuscitative
facilities (including medications) and personnel
trained to evaluate and treat serious adverse
reactions be available.

67. Iron during infection.
• Avoid administering IV iron to
patients with active systemic
infections. (Not Graded)

68. Use of ESAs and other agents to treat anemia
in CKD
•ESA initiation
•ESA maintenance therapy
•ESA dosing
•ESA administration
•Type of ESA

69. ESA initiation
• Address all correctable causes of anemia (including iron
deficiency and inflammatory states) prior to initiation of
ESA therapy. (Not Graded)
• In initiating and maintaining ESA therapy, we recommend
balancing the potential benefits of reducing blood
transfusions and anemia-related symptoms against the
risks of harm in individual patients (e.g., stroke, vascular
access loss, hypertension). (1B)

70. •We recommend using ESA therapy with great
caution, if at all, in CKD patients with active
malignancy—in particular when cure is the
anticipated outcome—(1B), a history of stroke
(1B), or a history of malignancy (2C).
• For adult CKD ND patients with Hb
concentration Z10.0 g/dl (Z100 g/l), we suggest
that ESA therapy not be initiated. (2D)

71. •For adult CKD ND patients with Hb concentration
o10.0 g/dl (o100 g/l) we suggest that the decision
whether to initiate ESA therapy be individualize
based on the rate of fall of Hb concentration, prior
response to iron therapy, the risk of needing a
transfusion, the risks related to ESA therapy and the
presence of symptoms attributable to anemia. (2C)

72. •For adult CKD 5D patients, we suggest that ESA
therapy be used to avoid having the Hb
concentration fall below 9.0 g/dl (90 g/l) by
starting ESA therapy when the hemoglobin is
between 9.0–10.0 g/dl (90–100 g/l). (2B)
•Individualization of therapy is reasonable as
some patients may have improvements in
quality of life at higher Hb concentration and ESA
therapy may be started above 10.0 g/dl (100
g/l). (Not Graded)

73. •For all pediatric CKD patients, we suggest that
the selection of Hb concentration at which
ESA therapy is initiated in the individual
patient includes consideration of potential
benefits (e.g., improvement in quality of life,
school attendance/performance, and
avoidance of transfusion) and potential harms.
(2D)

74. ESA MAINTENANCE THERAPY
• In general, we suggest that ESAs not be used to
maintain Hb concentration above 11.5 g/dl (115g/l) in
adult patients with CKD. (2C)
• indIvidualization of therapy will be necessary as some
patients may have improvements in quality of life at Hb
concentration above 11.5 g/dl (115 g/l) and will be
prepared to accept the risks. (Not Graded)

75. •In all adult patients, we recommend that
ESAs not be used to intentionally increase
the Hb concentration above 13 g/dl (130 g/l).
(1A)
• In all pediatric CKD patients receiving ESA
therapy, we suggest that the selected Hb
concentration be in the range of 11.0 to 12.0
g/dl (110 to 120 g/l). (2D)

76. ESA dosing.
•We recommend determining the initial ESA dose
using the patient’s Hb concentration, body weight,
and clinical circumstances. (1D)
•We recommend that ESA dose adjustments be made
based on the patient’s Hb concentration, rate of
change in Hb concentration, current ESA dose and
clinical circumstances. (1B)

77. •We suggest decreasing ESA dose in preference
to withholding ESA when a downward
adjustment of Hb concentration is needed.
(2C)
•Re-evaluate ESA dose if (Not Graded):K The
patient suffers an ESA-related adverse eventK
The patient has an acute or progressive illness
that may cause ESA hyporesponsiveness

78. ESA ADMINISTRATION.
•Frequency of administration
Determining the frequency of ESA
administration based on CKD stage,
treatment setting, efficacy considerations,
patient tolerance and preference, and type
of ESA.

79. •For CKD 5HD patients and those on
hemofiltration or hemodiafiltration therapy,
either intravenous or subcutaneous
administration of ESA. (2C)
•For CKD ND and CKD 5PD patients, we
suggest subcutaneous administration of
ESA. (2C)

80. Type of ESA.
• Choosing an ESA based on the balance of
pharmacodynamics, safety information, clinical
outcome data, costs, and availability. (1D)
•Using only ESAs that have been approved by an
independent regulatory agency. Specifically for
‘copy’ versions of ESAs, true biosimilar products
should be used. (2D)

81. Thank you!