1) The document discusses the approach to chronic kidney disease (CKD). It defines CKD and outlines its stages based on glomerular filtration rate and albuminuria levels. 2) Risk factors for CKD mentioned include diabetes, hypertension, family history of kidney disease, use of certain medications, and prior acute kidney injury. The pathogenesis of CKD involves initial injury followed by adaptive hyperfiltration and long-term damage to remaining nephrons. 3) Evaluation of patients with suspected CKD involves obtaining a history, physical exam, lab tests including serum creatinine and urine analysis, and imaging like renal ultrasound. A kidney biopsy may be done if disease-specific therapy is still possible.

1. APPROACH TO CHRONIC
KIDNEY DISEASES
Dr. Beka Aberra
Internal Medicine Resident
R1
2/16/2018 1

2. OUTLINE
1. Definition and Stages of CKD
2. Epidemiology of CKD
3. Risk factors for CKD
4. Pathogenesis of CKD
5. Approach to CKD
6. Complications of CKD
7. Principles of CKD Management
Treatment to delay progression
Treatment of complications
2/16/2018 2

3. 1. Definition and Stages of CKD
2/16/2018 3

4. Stages of Chronic Kidney Disease –NKF-K/DOQI
Stage Description
GFR
(ml/min/1.73
m2)
1
Kidney Damage with Normal or 
GFR
>90
2 Kidney Damage with Mild  GFR 60-89
3 Moderate  GFR 30-59
4 Severe  GFR 15-29
5 Kidney Failure
<15 or
Dialysis
2/16/2018 5

5. CKD- KDIGO 2012 Definition and Staging
•CKD is defined as:
Remains same except for the addition of
“With Implications for Health.”
Abnormalities of kidney structure or
function present for > 3 months
with implications for health
2/16/2018 6
Chronicity is not synonymous with irreversibility

8. CKD Classification/Staging : KDIGO 2012
• Recommend that CKD is classified based on Cause, GFR category, and
Albuminuria category (CGA)
2/16/2018 7

9. Evaluation of Albuminuria
• Albuminuria staging has been added because of the
graded increase in risk for mortality, progression of
CKD, and ESRD at higher levels of albuminuria,
independent of eGFR.
• 24hr-Urine-albumin is the Standard measurement
• Protein-to-creatinine ratio:
• Done from spot first-morning urine sample
• Correlates well, but not as perfect as 24hr determination
2/16/2018 10

10. CKD Classification/Staging : KDIGO 2012
2/16/2018 8

11. CKD Classification/Staging : KDIGO 2012
The relationship between urine reagent strip results and other measures depends on
urine concentration.
2/16/2018 9

12. Abnormal Sediments;
Histology
• Granular casts
• White blood cell cast
• Red blood cell cast

13. CKD Classification/Staging : KDIGO 2012
2/16/2018 11

14. 2/16/2018 12

15. Glomerular Filtration Estimation
Glomerular filtration rate (GFR) is generally accepted as the best overall index of
kidney function.
•GFR ~ 120 ml/min Declines naturally with age after ~40 (4-10ml/min/decade)
• KDIGO refers to a GFR <60 ml/min/1.73 m2 as Decreased GFR and
to a GFR <15ml/min/1.73 m2 as kidney failure.
Measured using Substance that's Filtered, Non-secreted and Non-metabolized
compounds
Inulin
Cr labelled EDTA
Radiocontrast e.g. Iohexol
 Creatinine is freely filtered but 15% actively secreted.
1/19/2018 19

16. Glomerular Filtration Rate
2/16/2018 20
The sum of Filtered Load (GFR X P),
Tubular Secretion (TS), and
Tubular Reabsorption(TR).
Generation (G)
Extra renal elimination (E)
Generation (G)
Urinary excretion (UV)
The plasma level (P) of an
endogenous filtration marker

17. • Measurement of GFR is complex, time consuming, and
cumbersome to do in clinical practice.
• GFR is measured by determining the urinary clearance of an
ideal filtration marker (completely filtered, not metabolized,
reabsorbed or secreted)
• Inulin is the gold standard filtration marker, but iothalamate and
iohexol are less cumbersome.
• The most common methods utilized to estimate the GFR are:
measurement of the creatinine clearance and estimation
equations.
Glomerular Filtration Rate
[Measurement vs Estimation]

18. Standard method for decades but not a reliable marker
It is a product of metabolism of creatine and phosphocreatine
It is freely filtered across the glomerulus but approximately 10 - 40 % of
urinary Cr is derived from tubular secretion.
Creatinine rises with falling GFR but the relationship between GFR and
serum Cr
Is not linear
Non renal elimination increased in CKD
Cr remains in “normal range” until GFR < 50%
Cr is influenced by diet
Influenced by drugs - trimethoprim
Affected by muscle mass, age, sex, race
Glomerular Filtration Creatinine Based

19. •Creatinine clearance
• Can be calculated with 24 hour urine and a blood draw
CrCl = UCr (mg/dl) x Uvolume (ml)
(SCr (mg/dl)) (1440)
oThe Cr clearance exceeds the true GFR by ~10 -20% or more
since part of the urinary Cr is derived from tubular secretion.
oUsing Cr clearance to estimate GFR is limited by errors in urine
collection and variation in the degree of Cr secretion.
Glomerular Filtration Measurement

20. 20
Estimation of GFR
1. Cockcroft-Gault
Equation
(mL/min) For women Multiply by 0.85
2. MDRD study equation
(mL/min/1.73 m2)
GFR = 186.3 x (SCr)−𝟏.𝟏𝟓𝟒
x (Age) − 𝟎.𝟐𝟎𝟑
Multiply by 0.742 for women
Multiply by 1.21 for African ancestry
3. CKD-EPI equation GFR = 141 × min( SCr
κ )α× max ( SCr
κ )−𝟏.𝟐𝟎𝟗× 0.993 𝒂𝒈𝒆
Multiply by 1.018 for women
Multiply by 1.159 for African ancestry
κ is 0.7 for females and 0.9 for males, α is –0.329 for females and –0.411 for males,
min indicates the minimum of SCr/κ or 1, & max indicates the maximum of SCr/κ or
1
(140 − age) x LBW [kg]
Cr [mg/dL] x 72
CCr =

21. (from Harrison 19E)

22. CKD-EPI vs MDRD equations
• CKD-EPI is superior over MDRD when GFR is normal or
mildly reduced (i.e. 60ml/min or above)
• CKD-EPI results in lower prevalence of CKD and better risk
prediction
• The performance at lower GFR and precision is not different
between the two formulae .
• Given the data on the improved performance, especially at
higher levels of GFR, using the CKD-EPI equation is
suggested

23. GFR estimating equations using:
Cystatin C
•It is suggested to use Cystatin C than Cr
based eGFR equations in adults with eGFR
45-59 ml/min/1.73m2 who do not have
markers of kidney damage, if confirmation
of CKD is required.

24. • Early diagnosis of CKD and identification of those likely to progress to End-
Stage Renal Disease (ESRD) has become highly important. Existing
measures including Creatinine level, estimated Glomerular Filtration Rate
(eGFR) and Proteinuria seem to be insufficient.
• Due to the development of Genomics, Epigenetics, Transcriptomics,
Proteomics, and Metabolomics, the introduction of novel techniques will
allow for the identification of novel biomarkers in renal diseases.
• Asymmetric dimethylarginine (ADMA), Symmetric dimethylarginine
(SDMA), Uromodulin, Kidney injury molecule-1 (KIM-1), Neutrophil
gelatinase-associated lipocalin (NGAL),
• miRNA, ncRNA, and lincRNA biomarkers and proteomic and metabolomic
biomarkers.

25. 2. Epidemiology of CKD
• The true incidence and prevalence of CKD within a community are difficult
to ascertain because early to moderate CKD is usually asymptomatic.
• Various epidemiologic studies suggest a prevalence of CKD of approximately
10% to 14% in the general population, Albuminuria( A2) of approximately
7% and GFR <60ml/min of 3%.
• USA at least 6% of the adult population has CKD at stages 1 and 2; additional
4.5% is estimated to have stages 3 and 4 CKD.
• Worldwide public health problem: “silent epidemic “
• Ethiopia???
25

26. Prevalence of Chronic Kidney Disease and Associated Risk Factors
among Diabetic Patients in Southern Ethiopia
• Done at Butajira Hospital, among adult diabetic patients on chronic follow up
• 23.8% of the study participants were found to have CKD
• 22.9% have stage 3 CKD, and
• 0.9% have stage 4 CKD
• Risk factors for CKD were similar to those reported in developed country
studies

27. CKD IN AFRICA
• South Africa
• Hypertension – affects approximately 25% of the adult
• Hypertension is the cause of 21% of ESRD
• Diabetic nephropathy 15%
•24% Zambia, 12.4% Egypt, 9% Sudan, 6% Ethiopia
• Cameroon - referral patterns to nephrology
• Risk factors for CKD 61% hypertension, 26% DM
• 82% referred GFR<30ml/min

28. 3. Risk factors for CKD
28

29. Adaptive hyper filtration
( PGC   SNGFR  wall stress   TGFß)
Initial injury
(GN, DM, ATN, AIN, PCKD)

Loss of renal parenchyma


Long-term damage
to remaining nephrons

Proteinuria,
progressive renal insufficiency 29
4. Pathophysiology

32. 5. Approach
• History
• Hypertension
• Diabetes Mellitus
• Abnormal urinalyses and
• Problems with pregnancy (Preeclampsia or early pregnancy loss)
• Drug use (NSAID, Chemotherapeutic Agents, PPI, ART)
• Family history of kidney disease (heritable form of CKD e.g., Alport or Fabry disease)
32

33. Approach
• Physical Examination
• Evaluation of
• Blood pressure and target organ damage from hypertension.
• Fundoscopy and precordial examination (LV heave, S4)
• Pericardial friction rub
• Asterixis
• Edema and sensory polyneuropathy
33

34. Approach
• Laboratory Investigations and Imaging
• CBC
• Urinalysis:
• Urine dipstick & microscopic exam
• 24hr Urine Protein
• Blood chemistry and Serology
• SCr, BUN, Coagulation profile
• Electrolytes (Na+, K+, CO2, Ca++, P),
• ANA, C3, C4,
• HBsAg, HCV Ab
• PTH
34
• Serum Iron, vitamin B12, and folate levels.
• ACR
• GFR:
• Renal Ultrasound
• Bilateral shrunken kidneys with cortical
thinning
• Increased echogenicity
• Doppler sonography,
• Nuclear medicine studies
• CT or MRI studies.

35. Approach
• Kidney Biopsy
• Not advised in patient with bilaterally small kidneys, b/c
• It is technically difficult & has a greater likelihood of causing bleeding
• So much scarring that the underlying disease may not be apparent, and
• The window of opportunity to render disease-specific therapy has passed.
• Contraindications:
• Uncontrolled hypertension,
• Active urinary tract infection,
• Bleeding diathesis (including ongoing anticoagulation)
35

36. Evaluation (KDIGO)
1. Evaluation of Chronicity
• GFR <60 ml/min/1.73 m2 or Markers of kidney damage.
• Review past history & previous measurements to determine duration of kidney
disease.
• Duration is >3 months, CKD is confirmed..
• Duration is <3 months or unclear, CKD is not confirmed.
• Patients may have CKD or AKI or both and tests should be repeated
accordingly. 36

37. AKI-CKD
•AKI-on-CKD is critical to consider because
patients with CKD are at risk for many of the
conditions causing AKI ,and AKI may be
associated with more rapid progression to ESRD
AKI CKD
2/16/2018 37

38. AKI
•Recent acute illness
•Recent decline in
urine output
•Fluid overload
•Normal sized kidneys
CKD
Anemia,
Calcium-phosphate
abnormalities,
Malnutrition
Previous history of abn urinary
sed, decreased GFR
Renal osteodystrophy
High cr. With normal urine vol.
or stable looking pts
Small, shrunken kidneys
2/16/2018 38
AKI-CKD

39. Evaluation (KDIGO)
2. Evaluation of cause
• Personal and family history,
• Social and Environmental factors,
• Medications,
3. Evaluation of GFR
• Use serum creatinine and a GFR estimating equation for initial assessment.
• eGFR should be reported the units ml/min/1.73 m2
39
• Physical examination,
• Laboratory measures, Imaging, and
• Pathologic diagnosis

40. Evaluation (KDIGO)
4. Evaluation of albuminuria
• Use the following measurements for initial testing (descending):
• Urine albumin-to-creatinine ratio (ACR);
• Urine protein-to-creatinine ratio (PCR);
• Urinalysis strip for TP with automated reading;
• Urinalysis strip for TP with manual reading.
40
Albuminuria
Category
Protein reagent
strip
A1 Negative to trace
A2 Trace to +
A3 + or greater

41. 6. Major complications of CKD
• Cardiovascular disease
• Anemia
• Mineral bone disease
• Malnutrition
• Fluid overload
• Acid base disorders
• Electrolyte disorders(Hyperkalemia, hyponatremia)
• Uremia
2/16/2018 48

42. Complications
42
“ADMA” is considered to be the “missing
link” between cardiovascular disease and
CKD

43. Cardiovascular Complications
• Leading cause of morbidity and mortality in patients at every stage of CKD
• Albuminuria is now recognized as a major risk factor for cardiovascular disease.
• 10 to 200 fold increased risk compared to age- and sex-matched general population
• Most patients with CKD Succumb to CV disease before ever reaching stage 5 CKD.
• N.B. Focus of patient care in earlier CKD stages should be directed to prevention of
cardiovascular complications
43

44. Cardiovascular Complications
• Ischemic Vascular Disease
• Any stage of CKD is a major risk factor for IHD, CVD, and PAD
• Involves interplay of both “Classic” and “CKD-related” risk factors.
• Hemodialysis hypotension and hypovolemia, may further aggravate coronary
ischemia and repeatedly stun the myocardium.
• Cardiac troponin levels are frequently elevated in CKD w/o evidence of acute
ischemia.
• complicates the diagnosis of acute myocardial infarction
44

45. Cardiovascular Complications
• Abnormal cardiac function 20 to myocardial ischemia,
• LV hypertrophy, and frank cardiomyopathy,
• Salt and water retention
45
Heart Failure &
Pulmonary edema.
• Rx. Lifestyle changes, including regular exercise.
• Management of hyperlipidemia.
• Dietary measures,
• if not enough statins (Atorvastatin, simvastatin)

46. Cardiovascular Complications
• Hypertension
• One of most common complications (usually develops early (80-85%))
• Associated with adverse outcomes
• development of LVH and more rapid loss of renal function
• Absence of hypertension may signify poor left ventricular function.
• low BP actually carries a worse prognosis than does high BP.
• Systolic BP is the recommended target,
• it correlates better with CKD progression than diastolic BP
46

47. Cardiovascular Complications
• Target BP: <140/90 Vs. <130/80.
• the greater the proteinuria, the greater the benefit of the low BP goal
• Rx. Slows the progression of CKD & reduce the rate of CV complications.
• Salt restriction should be the first line of therapy (<2 g/day)
• If the systolic BP is >20 mm Hg above goal, ≥2 antihypertensive agents will usually be
needed.
• ACEIs and ARBs slow the rate of decline of kidney function.
• Combination didn’t show any benefit over either used alone
• NDHP-CCB class of agents, are anti-proteinuric and may be Reno protective.
• Avoid Dihydropyridine Calcium Channel Blockers as first line therapy
• Potassium-sparing diuretics should be used with caution or avoided in most patients.
47

48. Begin with ACE inhibitor or ARB therapy
BP goal: Systolic BP in the 120s mm Hg or less if tolerated
If BP not at goal after 2–4 weeks, titrate ACE inhibitor (or ARB) upward to maximally recommended dose
If proteinuria is low level (e.g., 24-hr urine PCR <0.6, ACR <0.4);
add amlodipine
If proteinuria is higher level add an NDHP-CCB
If BP not at goal after 2 to 4 weeks
If BP not at goal after 2 to 4 weeks, an individualized approach is suggested.
Add aldosterone antagonist, especially if
• Diabetic mellitus
• Serum K+ tends to be at the low end of normal
Add diuretic especially if:
• African ancestry
• Habitual high salt intake
• Edema-forming state

49. Cardiovascular Complications
• Pericardial Disease
• Chest pain with respiratory accentuation, accompanied by a friction rub
• ECG
• PR-interval depression and diffuse ST-segment elevation
• observed in advanced uremia
• An absolute indication for the urgent initiation of dialysis
• for intensification of the dialysis prescription in those already receiving dialysis
• Hemodialysis should be performed without heparin
49

50. Anemia
Kidneys secrete 90% of erythropoietin
Declining kidney function leads to erythropoietin deficiency.
Mild anemia can be asymptomatic
Patients with more severe anemia may experience fatigue, weakness,
shortness of breath
Anemia treatment may improve/resolve symptoms
 may stabilize kidney function
Erythropoietin stimulating agents used to correct anemia
502/16/2018

51. • Hgb. concentration is <13.0 g/dl in males and <12.0 g/dl in females.
• Normocytic, Normochromic anemia
• Observed as early as stage 3 CKD and is almost universal by stage 4.
• Causes:
• Relative deficiency of erythropoietin
• Diminished red blood cell survival
• Bleeding diathesis
• Iron deficiency 51
• Hyperparathyroidism/bone marrow fibrosis
• Chronic inflammation
• Folate or vitamin B12 deficiency
• Hemoglobinopathy
Anemia

52. Treatment: Anemia (target: Hemoglobin 10- 11.5gm/dl)
• Recombinant human EPO and modified EPO products, such as
Darbepoetin-alpha has long half-life
• Adequate bone marrow iron stores should be available before
treatment with EPO is initiated b/c Iron supplementation is essential
for optimal response to EPO in CKD.
• Adequate supply of other major substrates and cofactors for red cell
production like vitamin B12 and folate.
• EPO Complications???
2/16/2018 52
Anemia

53. • Target: ≥ 11.5 g/dl
53
Anemia of CKD
Exclude causes other than EPO deficiency
(e.g., iron, B12, folate deficiency)
If ferritin <100 µg/l, consider trial
of IV iron alone, 200–500 mg
If ferritin >100 µg/l or no response to IV iron,
start EPO, 4000–6000 IU/wk or darbepoetin alfa
20–30 µg/wk
Adjust ESA dose by 25%–50% monthly
until Hb in target range of 11–13 g/dl
Maintain iron status according to….
Test Recommended Range
Serum Ferritin
100 - 500 µg/l (CKD)
200 – 500 µg/l (HD)
Transferrin
Saturation
20 - 40%
Hypochromic Red
cells
<10%
Reticulocyte
hemoglobin
content (CHr)
>29 pg/cell

54. 2/16/2018 54
•Blood transfusions
• Increase the risk of
• Hyperkalemia
• Iron overload
• Transplant sensitization
. Should be avoided unless the anemia fails to respond
to EPO and the patient is Symptomatic.
Anemia

55. CKD-MBD
A systemic disorder of mineral and bone metabolism due to CKD
manifested by either one or a combination of the following:
 Abnormalities of calcium, phosphorus, Magnesium, PTH, FGF-23 or
vitamin D metabolism
 Abnormalities in bone turnover, mineralization, volume, linear
growth, or strength
 Vascular or other soft tissue calcification
• Renal osteodystrophy is an alteration of bone morphology in patients
with CKD, used exclusively to define the bone disease associated with
CKD.
• CKD-MBD defined as more broader clinical, biochemical and imaging
abnormalities identified as correlates of renal osteodystrophy.

56. Pathogenesis of Disordered Mineral Metabolism
in Chronic Kidney Disease
Phosphorus retention
Low calcitriol levels
Secondary Hyperparathyroidism
and
Parathyroid gland hyperplasia
Hypocalcemia
Skeletal resistance
to PTH
↓ GFR
↑ PO4
↓1,25(OH)2D
↑ 7-84 PTH
↓ Renal mass
↑ FGF23
Hyperphosphatemia
P = Phosphorus
PTH = Parathyroid Hormone
FG23 = Fibroblastic Growth Factor 23
GFR = Glomerular Filtration Rate
CKD-MBD

57. Spectrum of Renal Osteodystrophy
Calcium, Calcitriol (Vit D), Al3+
PTH
High Bone
TurnoverLow Bone
Turnover
Normal bone
formation
Adynamic BD;
Osteomalacia
Mild Osteitis
Fibrosa
Mixed lesion
<150 pg/mL 150-300 pg/mL >300-400 pg/mL
From Goodman WG.
Sherrard DJ, et al. Kidney Int. 1993;43:436-442.
Wang M, et al. Am J Kidney Dis. 1995;26:836-844.
CKD-MBD

58. Osteitis Fibrosa
(HyperParathyroid Bone Disease)
• Clinical manifestations of severe hyperparathyroidism include bone
pain and fragility, brown tumors (focal collections of giant cells seen
as well-demarcated radiolucent zones sometimes with hemorrhagic
elements )
• ↑PTH(≥600 pg/ml)
• ↑ALP(BAP) is a marker of bone formation
• X-ray and Biopsy
• Optimal Mgt of Osteitis fibrosa is Prevention ,and should Start at
Stage 3
2/16/2018
58

59. Hyperphosphatemia: Treatment
• Dietary Phosphate restriction
• Phosphate binders include Calcium containing binder [Ca
carbonate or acetate]
• Non Calcium Containing Binders [Sevelamer and
Lanthanum Carbonate]
• Para thyroidectomy for limited indications
2/16/2018 59
Hyperphosphatemia

60. • Adynamic bone disease : Reduced Bone Volume and Mineralization,
result from excessive suppression of PTH production, (PTH <100
pg/ml)
-Suppression of PTH can result from the use of vitamin D preparations
or from excessive calcium exposure (calcium- containing phosphate
binders or dialysis solutions)
• Complications : - increased incidence of fracture; increased vascular
and cardiac calcification ; Ca may precipitate in the soft tissues into
large concretions termed “tumoral calcinosis”
• Rx - Restore adequate PTH (↓ Vit D, Ca)
2/16/2018 60
Adynamic Bone Disease

61. 2/16/2018 61
CKD-MBD
Vascular and soft tissue
calcification

62. 62
Elevated:
• FGF-23
• PTH
• Phosphorus
Decreased:
• Calcitriol
• Calcium
• Coronary
calcification
• Aortic calcification
• Calciphylaxis
• Abnormal bone
histology
–Mineralization
–Turnover
–Volume
• Decreased bone
mineral density
KDIGO = Kidney Disease: Improving Global Outcomes.
CKD-MBD

63. Anorexia & Malnutrition
NKF K/DOQI guidelines: Evaluate for signs of
malnutrition when GFR < 60 mL/min/1.73 m2
[Stages 3, 4, 5]
Protein-energy malnutrition due to
-decreased intake; decreased absorption
-inflammation; metabolic acidosis
*Is an indication for initiation of renal replacement
therapy.
63

64. Abnormal Hemostasis
• Prolonged bleeding time, decreased activity of platelet factor III,
abnormal platelet functions aggregation & adhesiveness → Bleeding
• Nephrotic-range proteinuria → hypoalbuminemia and renal loss of
anticoagulant factors → Thromboembolism
• Treatment
- Coagulopathy reversed by desmopressin (DDAVP), cryoprecipitate,
IV conjugated estrogens, blood transfusions, and EPO therapy.
- Decision to anticoagulate should be made on an individual basis in
CKD patient due to risk of bleeding.
-RRT
2/16/2018 64

65. Neuromuscular Abnormalities
• Subtle c/m starts at stage 3 ckd ; mild disturbances in memory and concentration
and sleep disturbance.
• Neuromuscular irritability, including hiccups, cramps, and fasciculation's or
twitching of muscles, becomes evident at later stages
• Advanced untreated kidney failure → asterisks, myoclonus, seizures, and coma
• Peripheral neuropathy mostly at stage 4 CKD
 Sensory more than motor, lower extremities more than upper, and distal
parts of the extremities more than proximal.
 Restless leg syndrome" ; ill-defined sensations of legs and feet relieved by
frequent leg movement
 Evidence of peripheral neuropathy without another cause (e.g., DM) is
indication for starting RRT
2/16/2018 65

66. Gastrointestinal
• Uremic fetor, a urine-like odor on the breath, derives from the
breakdown of urea to ammonia in saliva
• Uremic fetor with an unpleasant metallic taste (Dysgeusia)
• Gastritis and mucosal ulcerations→ pain, nausea, vomiting, and GI
bleeding
• Uremic toxins also leads to anorexia, nausea, and vomiting
2/16/2018 66

67. • Glucose metabolism is impaired in CKD
• FBS is usually normal or only slightly elevated, and does not require specific therapy.
• Plasma levels of insulin are slightly to moderately elevated.
• Patients on insulin therapy may need progressive reduction in dose as their renal function worsens.
• OHA agents such as Metformin, are contraindicated when GFR is less than half of normal.
• In women with CKD,
• Estrogen levels are low, & menstrual abnormalities, infertility, and preterm deliveries are common.
• GFR ~40 mL/min, pregnancy is assoc. with a high rate of spontaneous abortion.
67
Endocrine-metabolic Disturbances

68. Dermatologic
• Pruritus
Mgt - Hyperphosphatemia, can cause it, so should be R/O
- Local moisturizers, mild topical glucocorticoids, oral
antihistamines, and ultraviolet radiation.
• Hyperpigmentation→ reflect the deposition of retained pigmented metabolites, or
urochromes.
• Nephrogenic Fibrosing Dermopathy
-Progressive subcutaneous induration, especially on the arms and legs seen in
patients with CKD who have been exposed to the MRI Contrast Agent Gadolinium
-Unique to CKD patients; CKD stages 4–5 (GFR <30 mL/min) should avoid the use of
gadolinium agents unless it is medically necessary.
2/16/2018 68

69. Uremia
The word uremia is generally used to describe those ill
effects of advanced renal failure that we cannot yet explain.
Hypertension due to volume overload, tetany due to
hypocalcemia, and anemia due to erythropoietin deficiency
were once considered uremic signs but were removed from
this category as their causes were discovered.
In the present state of knowledge, uremia may thus be
defined as the illness that would remain if the extracellular
volume and inorganic ion concentrations were kept normal
and the known renal synthetic products were replaced in
patients without kidneys .

70. Hundreds of toxins that accumulate in Renal failure
have been implicated as cause for uremic syndrome.
Including Guanidino cpds, Urates, hippurates,
polyamines, phenols, myoinositols.
Metabolic and Endocrine functions of kidney
Derangements..
Plasma levels of insulin ,glucagon, PTH, prolactin change
due to retention, or decreased degradation.
Uremia

71. Uremia Features
Neural and muscular
Fatigue
Loss of concentration ranging to coma
and seizures
Sleep disturbances
Anorexia and nausea
Diminution in taste and smell
Cramps
Restless legs
Peripheral neuropathy
Reduced muscle membrane potential
Endocrine and metabolic
Amenorrhea and sexual dysfunction
Reduced body temperature
Reduced resting energy expenditure
Insulin resistance
Other
Serositis (including pericarditis)
Pruritus
Hiccups
Granulocyte and lymphocyte dysfunction
Platelet dysfunction
Shortened erythrocyte life span
Albumin oxidation

72. 7. Principles of CKD Management
Optimal management
•Delaying progression
•Treatment of Comorbidities
•Treatment of Complications
•Transition to End Stage Renal Disease

74. Early Detection and
Screening
• Different guideline at different
countries.
• Screening should consist of
• Urinalysis,
• Urine albumin/protein estimation
• Measurement of SCr & estimation
of GFR
• Preferably by the CKD-EPI equation 74

75. Early Treatment Makes a Difference
Brenner, et al., 2001
*Obtain minimum 3 GFRs over not less than 90 days
If new finding low GFR, repeat within 2 weeks to
exclude ARF

76. Treatment of Reversible Causes
• Any acceleration in the rate of decline should prompt a
search for superimposed acute or sub acute processes that
may be reversible.
• ECFV depletion,
• Uncontrolled hypertension,
• Urinary tract infection, sepsis
• Exposure to nephrotoxic agents
• Reactivation or flare of the original disease (lupus or vasculitis.)
• Urinary tract obstruction
2/16/2018 76

77. Slowing progression
Progression
• Small fluctuations in GFR are common and are not indicative of
progression.
• A certain drop in eGFR (defining progression) -is defined as a drop in
GFR category accompanied by a 25% or greater drop in eGFR from
baseline.
• Rapid progression is defined as a sustained decline in eGFR of more
than 5 ml/min/1.73 m2/year.
2/16/2018 77

78. General measures
Smoking cessation
Moderation of alcohol use
Physical activity , Weight reduction
Protein restriction
• daily protein intake of 0.8g/kg per day when GFR<30 & avoid high proten
>1.3g/24 hr in CKD
Salt restriction
• lowering Na intake to <2 g/day
2/16/2018 78
How to slow progression

79. Control of systemic & intraglomerular HTN
and Proteinuria
ACE inhibitors and ARBs─ first line
to reduce proteinuria.
 ACEI/ARBs- in diabetic adults
with CKD and urine albumin
excretion 30–300 mg/24 hours
and in both diabetic and non-
diabetic adults with CKD and
urine albumin excretion >300
mg/24 hours
ACEI/ARBs
2/16/2018 79

80. • Calcium channel blockers
• Diltiazem and verapamil exhibit superior antiproteinuric and Reno protective
effects.
• DHP [Amlodipine..] ↑proteinuria
• Loop diuretics if edema presents →concomitant use of a kaliuretic
diuretic, such as metolazone, can improve potassium excretion
• Aldosterone antagonists /spironolactone
Used with caution added to an ACE inhibitor and/or ARB
• Other antihypertensive drugs have little or no effect
on protein excretion.
2/16/2018 80

81. Control of Blood Glucose
• Excellent glycemic control reduces the risk of kidney disease and its
progression.
• Recommended that
• Hemoglobin A1C should be 7%.
• As the GFR decreases with progressive nephropathy, the use and
dose of oral hypoglycemics /insulin needs to be reevaluated.
2/16/2018 81

82. Managing dyslipidemia
• Patients with CKD stage 3 frequently develop dyslipidemia.
• Statin therapy may benefit patients with CKD stage 3 with vascular
disease,
• There is no robust evidence to suggest that these drugs benefit
• CKD patients without overt vascular disease or
• Those with more advanced stages of CKD.
• Furthermore, the risks for myopathy with the use of fibrates and statins is
increased
2/16/2018 82

84. Managing Complications
Hypertension
• Present in ≥80% of those with advanced CKD.
• BP Target:
• <140/90mmHg (JNC 8) vs 130/80 mmHg (2017 AHA)
• ACR <30 mg/g: ≤140/90 mm Hg
• ACR 30-300 mg/g: ≤130/80 mm Hg* KDIGO
• ACR >300 mg/g: ≤130/80 mm Hg
• ACE-I, ARB, Non Dihydropyridine Ca channel blockers,
2/16/2018 84

85. Fluid and electrolyte disorders [Sodium and Water]
• Most Pt: (e.g. Glomerulonephritis) as ↓GFR
• Impaired Na excretion => Edema, HTN, CHF
• Rx:
• Na+ restriction
• Loop diuretics
• RRT
• In some patients:
• There is salt wasting due to impaired renal conservation of
sodium and water => volume depletion => worsening of
CKD
• Rx:
• Cautious volume repletion with NS
2/16/2018 85
Managing Complications

86. Fluid and Electrolyte Disorders [Hyperkalemia]
• Develops in advanced CKD
• Can occur earlier in patients with:
• Distal nephron d/s like Obstructive Uropathy
• Diabetic NP Hyporeninemic Hypoaldosteronism
• Drugs: as ACEI, Ang 2 R Antagonist, Beta-blockers, NSAIDs, K+ sparing diuretics,
Trimethoprim, Salt substitutes..
• Rx:
• Dietary K+ restriction,
• Loop diuretics,
• K+ exchange resins
• RRT
2/16/2018 86
Managing Complications

87. Fluid and Electrolyte Disorders [Acid-Base Disorders]
• Metabolic acidosis:
• Occurs due to failure of hydrogen ion excretion 20 less Ammonia.
• Accumulation of Organic acids and Bicarbonate loss.
• Treatment:
• Decrease protein intake
• Alkali supplementation if bicarbonate < 22mmol/L
• Na bicarbonate or Na citrate, (↑risk of fluid retention)
• This will prevent:
• Excessive bone loss
• Muscle breakdown
• Tubulointerstitial inflammation
• Progression of CKD and improved nutritional status
• Severe metabolic acidosis associated with symptoms in a patient with CKD
category G5 may be an indication to start dialysis.
2/16/2018 87
Managing Complications

88. Infections and Vaccination
•CKD is state of chronic immunosuppression
because of defects in both cellular and humoral
immunity.
•Infection is the second most common cause of
death after CVD in patients with ESRD.
•The risk of bacterial infection (Especially; Staph,
TB React.) increases with GFR.
2/16/2018 88

89. Medication Management
• Many drugs and investigative pharmaceuticals are renaly
excreted and their dosage may need to be reduced based on
the GFR in patients with CKD.
• No dose adjustment is needed if >=70% drug excretion is
extra renal.
• Some drugs that should be avoided include metformin
(GFR<30), meperidine, and oral hypoglycemics that are
eliminated by the kidneys, NSAIDs, and other nephrotoxic
drugs
2/16/2018 89

90. Renal replacement therapy
• Clinical indications to initiate dialysis in patients with CKD
• Uremic Pericarditis (urgent indication)
• Progressive uremic encephalopathy or neuropathy(urgent
indication)
• A clinically significant bleeding diathesis attributable to uremia
(urgent indication)
• Persistent metabolic disturbances that are refractory to medical
therapy( hyperkalemia, metabolic acidosis,)
• Fluid overload refractory to diuretics
• Persistent nausea and vomiting
• Evidence of malnutrition
2/16/2018
90

91. Referral to a Nephrologist
• GFR <30 ml/min/1.73 m2 (GFR categories G4-G5)
• Consistent finding of significant albuminuria(A3)
• Progression of CKD
• Urinary RBC casts ,sustained RBC>20/hpf, not otherwise readily
explained
• CKD and hypertension refractory to treatment with 4 or more
antihypertensive agents;
• Persistent abnormalities of serum potassium;
• Recurrent or extensive nephrolithiasis;
• Hereditary kidney disease.
2/16/2018 91

92. • Identify people with Chronic Kidney Disease. KDIGO 2012 Defn
• Assess and monitor Creatinine levels; estimated glomerular filtration
rate (eGFR) and Proteinuria.
• CKD and ESRD are increasing- Diabetes and hypertension are the
leading causes of ESRD.
• Urine albumin is a marker of kidney damage.- Control blood pressure
[Particularly with high urine albumin]; ACEi and ARBs may be
Antiproteinuric.
• Complications increase as kidney function declines [Anemia, CKD-
MBD, CVD, Fluid and Electrolyte Abn, Malnutrition, Uremia]
Take Home Message

93. • Reduce sodium intake to 1,500 mg; Good control of diabetes; Weight
reduction (if obese); Reduce protein intake, if excessive; Tobacco
cessation is important.
• The burden of kidney failure in Ethiopia is concealed behind statistics
that reflect only the number of people treated, not the number who die
of kidney failure.
• There should be registries to determine the true prevalence of kidney
disease in Ethiopia.
• Clinicians must focus on the early detection, prevention, and
management of kidney disease.
Take Home Message

94. Take Home Message
• Dialysis services will need to be affordable and very cost-effective by
using in-kind donations, government cooperation, and volunteerism.
Medical leaders should try to work with local policy makers,
business leaders, pharmaceutical companies, and clinicians to
develop population care management programs that focus on
education, early detection and effective treatment to prevent and
to slow down progression of kidney disease.

95. References
• KDIGO 2012 Clinical Practice Guideline for the Evaluation and
Management of Chronic Kidney Disease
• Harrisons principles of Internal Medicine 19th edition.
• Comprehensive clinical nephrology 5th edition
• KDIGO 2017 Clinical Practice Guideline Update for the Diagnosis,
Evaluation, Prevention, and Treatment of CKD-MBD
• Current Medical Diagnosis and Treatment, 2018, 57th Ed.
• Up to date 21.6
2/16/2018 95