Chronic kidney disease, also called chronic kidney failure, involves a gradual loss of kidney function. Your kidneys filter wastes and excess fluids from your blood, which are then removed in your urine. Advanced chronic kidney disease can cause dangerous levels of fluid, electrolytes and wastes to build up in your body.

1. CHRONIC KIDNEY DISEASE
& END-STAGE RENAL DISEASE
PALESTINE POLYTECHNIC UNIVERSITY
Faculty of Medicine and Health Sciences
MohmmadRjab Seder

2. A 29YO Woman & a 52YO Man
A 29-year-old woman is noted to have microscopic hematuria and 2+
positive-dipstick proteinuria (no proteinuria on dipstick is normal) on
screening labs for a life insurance policy. It was confirmed on a repeat
urinalysis 3 months later. Her serum creatinine is normal.
A 52-year-old man with a history of hypertension is noted to have a
serum creatinine of 1.7 mg/dL (normal 0.5-1.2 mg/dL). His urinalysis is
unremarkable. In review of his past records, his serum creatinine was
elevated to 1.7 mg/dL 6 months prior.
Which one of these patients has chronic kidney disease?

3. CHRONIC KIDNEY DISEASE
oAbbreviated as: CKD.
oAKA: Chronic Renal Failure.
oDefinition: a progressive decline in GFR (< 60 ml/min/1.73m2)
for at least 3 months or abnormal kidney structure/function.
oEnd-stage renal disease represents a stage of CKD

5. AETIOLOGIES OF CDK
30%
25%
15%
5%
25% Diabetes
HTN
Glomerulonephritis
PKD
Others

7. RISK FACTORS FOR CDK

8. DETECTINIG CKD
Individuals with risk factors for CKD
should undergo a Kidney Health
Check every 1-2 years.

9. PATHOPHYSIOLOGY

10. PATHOPHYSIOLOGY … HTN-CKD
Wall thickening in renal
artery
Narrow lumen
Less blood and O2 to
the kidney
Ischemic injury to
glomeruli and nephrons
Macrophages and
foam cells infiltration to
glomerulus
Growth factor (TGF-B1)
secretions
Mesangial cells progress
to mesangioblasts
Mesangioblasts secretes
ECM
Glomerulosclerosis
CKD
1
2
3 4
5
6 7
8
9
10

12. Progression of the
disease

13. Secondary glomerular changes associated with a reduction in nephron number, including enlargement of
capillary lumens and focal adhesions, which are thought to occur consequent to compensatory hyperfiltration
and hypertrophy in the remaining nephrons.

14. CLASSIFICATION OF CKD
Based on:
oThe GFR.
oThe presence of albuminuria.
oThe cause of kidney disease.
(ESRD)

15. THE RISK OF ADVERSE OUTCOMES IN CKD
can be represented as a ‘heat map’ according to GFR and albuminuria categories

16. MORPHOLOGY
GROSSLLY:
o Symmetrically contracted
o Red-brown surface
o Surface is diffusely granular
MICROSCOPICALLY:
o Advanced scarring of the glomeruli (Fig.)
o Interstitial fibrosis
o Atrophy and dropout of many tubules in the cortex
o Thick-wall arteries with narrow lumina secondary to HTN
o Lymphocytes infiltrates in the fibrotic interstitial tissue
Complete replacement of virtually all glomeruli by blue-staining collagen.

17. CLINICAL MANIFESTATIONS … (1)
1. Na+ and H2O balance
o ↓GFR → ↑ Na+ and H2O retention → ↑BP, peripheral oedema, CHF.
2. K+ balance
o ↓GFR → ↑K+ → muscle weakness, ECG changes, fibrillations.
o Loss of nephron → ↓Renin → ↓Aldosterone → distal Na+/K+ pump not
functional → K+ retention.
3. Metabolic acidosis
o ↓H+ excretion and ↓ammonia production → acidosis → bone decalcification.
4. Mineral balance and osteodystrophy
o Loss of nephrons → ↓calcitriol → ↓Ca+2 reabsorption → Hypocalcaemia →
secondary hyperparathyroidism → bone breakdown → renal osteodystrophy,
hyperphosphatemia (see next slide).

18. CLINICAL MANIFESTATIONS … (2)
Calciphylaxis
Hyperphosphatemia → calcium and phosphate precipitation → vascular
calcification → necrotic skin lesions.

19. CLINICAL MANIFESTATIONS … (3)
5. Other manifestations of uraemia
o Loss of nephrons → ↓urea excretion → uraemia (↑BUN, ↑serum Cr).
URAEMIC MANIFESTATIONS:
Neurological: cramps, lethargy, uremic seizures, encephalopathy.
GI: N&V, anorexia.
Reproductive: ↓oestrogen, ↓testosterone.
Immunologic: uraemia inhibits cellular and humoral immunity.
Haematologic: uraemia cause platelet dysfunction → Bleeding.
CVS: uremic pericarditis (results from metabolic toxins accumulation).
Skin changes and pruritis.

20. CLINICAL MANIFESTATIONS … (4)
6. Other manifestations due to loss of nephrons:
o ↓Renin → ↓BP
o ↓Epo → anaemia (normocytic normochromic)
o ↓Calcitriol → renal osteodystrophy

21. CLINICAL FEATURES
SYMPTOMS:
o Generally asymptomatic until GFR is < 30 mL/min.
o Patients gradually experience the signs and symptoms of electrolyte
disorders, uraemia, anaemia.
o Ammonia-smelling breath, and polyuria.
SIGNS:
o Hypertension
o Pruritus
o Nocturia
o Restless legs
o Haematuria
o Dyspnoea
o Lethargy
o Nausea/vomiting
o Malaise
o Anorexia

22. LABS
GFR (↓)
[Ca+2 ] (↓)
(Na+] (↓)
[HCO3-] (↓)
pH (↓)
Serum Cr (↑)
BUN (↑)
[K+] (↑)
[PO4-3] (↑)
PTH (↑)

23. LIFE-THREATENING
COMPLICATIONS IN CKD
oPULMONARY OEDEMA – secondary to volume overload.
oINFECTIONS – pneumonia, sepsis, UTI.
oHYPERKALAEMIA – obtain ECG.

24. DIAGNOSIS OF CKD
oHistory & physical examination.
oeGFR – Measure CrCl to estimate GFR.
oUrinalysis – proteinuria, …
oCBC – anaemia, thrombocytopenia.
oSerum electrolytes (e.g., K+, Ca+2, PO4-3) and serum protein.
oRenal USS – small kidneys.
oRenal biopsy – looks for glomerulosclerosis.
Clinical tip
CKD in itself is not a primary diagnosis. Attempts should be made to identify the
underlying cause of CKD.

25. STAGES OF CDK
Remember
(ESRD)

26. END-STAGE RENAL
DISEASE

27. ESRD
oESRD represents a stage of CKD where the accumulation of
toxins, fluid, and electrolytes normally excreted by the
kidneys leads to death unless the toxins are removed by renal
replacement therapy, using dialysis or kidney
transplantation.
oESRD is defined as that form of kidney failure so severe as to
need dialysis or renal transplantation.

28. MANAGEMENT OF CDK … (1)
Management of CKD requires:
1 Management to slow renal disease progression.
2 Management of renal complications of CKD.
3 Management of other complications of CKD.
4 Preparation for renal replacement therapy.

29. MANAGEMENT OF CDK … (2)
1 MANAGEMENT TO SLOW RENAL DISEASE PROGRESSION:
o BP – target systolic <140mmHg, diastolic <90mmHg.
(if DM or A:CR >70 then systolic target is <130mmHg and diastolic <80mmHg.)
o RAS – RAS antagonists:
o ACE-i – dilate efferent arteriole of glomerulus.
o ARB
o Glycaemic control – Target HbA1C of ~53mmol/mol (7.0%)
o Lifestyle modifications – low protein, low-salt diet, smoking cessation,
restrict potassium, phosphate, and magnesium intake. SNAP:
Smoking
Nutrition
Alcohol
Physical activity.

30. MANAGEMENT OF CDK … (3)
2 MANAGEMENT OF RENAL COMPLICATIONS OF CKD.
C BIG K

31. MANAGEMENT OF CDK … (4)
3 MANAGEMENT OF OTHER COMPLICATIONS OF CKD.
oCardiovascular disease
oAntiplatelets (low-dose aspirin)
o Atorvastatin 20mg (and higher if GFR >30) for primary and
secondary prevention of cardiovascular disease.
o Monitoring of [K+].

32. MANAGEMENT OF CDK … (5)
4 PREPARATION FOR RENAL REPLACEMENT THERAPY (RRT).
oRRT:
o Haemodialysis/ peritoneal dialysis.
oKidney transplantation.
oTransplantation is the only cure.

33. SYMMARY - CKD
oCHARACTERISTICS
o GFR < 60 ml/min/1.73 m2
for > 3 months.
o Abnormal function/structure.
oMOST COMMON CAUSES:
o DM
o HTN
oCOMPLICATIONS:
oElectrolyte abnormalities
o Toxins buildup
o HTN
o Weak bone
oDIAGNOSIS:
oMeasure eGFR.
oMeasure urine ACR.
oDetermine the underlying
pathology.
oMANAGEMENT
oSlow down disease progression.
oManage underlying cause.
oManage complications.
oPrepare for RRT.

34. PRACTICE … (1)
A 67-year-old woman is evaluated for painful skin lesions that have developed over the past 1-2 weeks. She has
longstanding end-stage renal disease, due to diabetic nephropathy, for which she undergoes hemodialysis 3 times a
week. Temperature is 37 C (98.6 F), blood pressure is 159/79 mm Hg, pulse is 97/min, and respirations are 16/min. Skin
examination findings are shown below. Laboratory results show elevated blood urea nitrogen, elevated serum
creatinine, and normal serum calcium. Punch biopsy of a lesion shows calcification of the middle layer of the
arterioles, subintimal fibrosis, and thrombotic occlusion without vasculitis. Which of the following is associated with an
increased risk for the painful skin lesions seen in this patient?
A. Hypermagnesemia
B. Hyperphosphatemia
C. Hypocalcemia
D. Recurrent hypoglycemia
E. Vitamin K excess

35. PRACTICE … (2)
A 68-year-old man is admitted with a left lower lobe pneumonia and is started on antibiotics. He has a long history of
diabetes, hypothyroidism, hypercholesterolemia, and hypertension. He also has diabetic retinopathy, peripheral
neuropathy, and nephropathy. He has an arterio-venous fistula placed for a possible dialysis. Medications are insulin,
furosemide, atorvastatin, metoprolol and levothyroxine. After having his blood drawn for some laboratory studies
today, he bleeds persistently. Laboratory studies show:
Hemoglobin 11.5 g/dl
Platelets 160,000/mm3
Blood glucose 178 mg/dl
Blood urea nitrogen 56 mg/dl
Creatinine 3.5 mg/dl
His baseline creatinine level is between 3.2-3.5 mg/dl. Which of the following is the most likely cause of his bleeding?
A. Disseminated intravascular coagulation
B. Platelet dysfunction
C. Factor VIII deficiency
D. Consumptive coagulopathy
E. Thrombocytopenia

36. ANSWERS
The two cases in slide 2: Both are CKD
Practice 1: B
Practice 2: B

37. REFERENCES
o Malkina, A., MD (2022). Chronic Kidney Disease. MSD Manual Professional.
https://www.msdmanuals.com/professional/genitourinary-disorders/chronic-kidney-disease/chronic-kidney-disease.
o Kasper, D. L., Fauci, A. S., Hauser, S. L., Longo, D. L., Jameson, J. L., & Loscalzo, J. (2018). Harrison’s Principles of Internal
Medicine 20/E (Vol.1 & Vol.2) (ebook). McGraw-Hill Education.
o Wilkinson, I. B., Wilkinson, I. B., Raine, T., Wiles, K., Goodhart, A., Hall, C., & O’Neill, H. (2017). Oxford Handbook of Clinical
Medicine. Oxford University Press.
o Agabegi, S. S., Duncan, M. D., & Chuang, K. (2019). Step-Up to Medicine. Wolters Kluwer.
o Le, T., & Bhushan, V. (2018). First Aid for the USMLE Step 2 CK, Tenth Edition. McGraw-Hill Education.
o (2018). Robbins Basic Pathology (10th ed.). ELSEVIER.

38. FOR FURTHER READING
The Chronic Kidney Disease (CKD) Management in Primary Care (4th edition) handbook
CLICK HERE

39. CANTACT