AKI, CKD, and ESRD are conditions involving the kidneys. AKI is a sudden loss of kidney function that develops over days or weeks and is often reversible. It is caused by prerenal factors like low blood pressure or intrinsic renal damage. Common causes include sepsis, low fluid intake, and medications. Diagnosis is based on increases in BUN and creatinine and decreased urine output. Treatment focuses on identifying and treating the underlying cause while managing fluid, electrolyte and acid-base imbalances. Long term kidney damage can progress to CKD or end stage renal disease requiring renal replacement therapies.

1. AKI, CKD, ESRD
Harrison Mbohe, MBChB Level 4

2. AKI
•AKI is not a single disease but rather, a designation
for a heterogeneous group of conditions that share
common diagnostic features: specifically, an increase
in the;
•Blood urea nitrogen (BUN) concentration and/or
•An increase in the plasma or serum creatinine
(SCr) concentration,
•Often associated with a reduction in urine volume

3. DEFINITION
•Sudden (develops over days or weeks) and often
reversible loss of renal function, usually
accompanied by a reduction in urine volume.
•Results in the retention of urea and other
nitrogenous waste products and in the
dysregulation of extracellular volume and
electrolyte.

4. AETIOLOGY

5. AETIOLOGY

6. RISK FACTORS
• Age >75 years
• Chronic kidney disease
• Cardiac failure
• Peripheral vascular disease (long standing HTN)
• Chronic liver disease
• Diabetes
• Drugs (especially newly started)
• Sepsis
• Poor fluid intake/increased losses
• History of urinary symptoms

7. PATHOGENESIS – PRE RENAL AKI
• Fall in perfusion pressure (hypovolemia and reductions in cardiac output):
Compensatory mechanisms:
• Renal vasoconstriction and salt and water reabsorption  maintenance of
blood pressure & increased intravascular volume  sustenance of
perfusion to the cerebral and coronary vessels. (mediated by angiotensin
II, norepinephrine, and vasopressin).
• Angiotensin II–mediated renal efferent vasoconstriction  maintenance
glomerular capillary hydrostatic pressure closer to normal  maintenance
of GFR
• A myogenic reflex within afferent arteriole  dilation in the setting of
low perfusion pressure  maintenance of glomerular perfusion.
(mediated by vasodilator prostaglandins (PGI2, PGE2), kallikrein,
kinins, and possibly NO).

8. PATHOGENESIS – PRE RENAL AKI
•Decreases in solute delivery to the macula densa 
dilation of the juxtaposed afferent arteriole  maintenance
of glomerular perfusion. (Tubuloglomerular feedback).
•There is a limit, however, to the ability of these counter
regulatory mechanisms to maintain GFR in the face of
systemic hypotension.
•Even in healthy adults, renal auto regulation usually fails
once the systolic blood pressure falls below 80 mmHg.

9. PATHOGENESIS – ACUTE TUBULAR NECROSIS
• Factors postulated to be involved in the development of ATN include:
• Intrarenal microvascular vasoconstriction – achieved via increased
vasoconstriction and impaired vasodilatation.
• Increased leucocyte–endothelial adhesion, vascular congestion and
obstruction, leucocyte activation and inflammation.
• Tubular cell injury results in rapid depletion of intracellular ATP stores
resulting in cell death either by necrosis or apoptosis.
• Tubular cellular recovery which involves rapid regeneration of tubular
cells and to reformation of the disrupted tubular basement membrane,
which involves a number of growth factors.

10. Acute tubular necrosis showing
• Effacement and loss of the
proximal tubule brush border
• Patchy loss of tubular cells
• Focal areas of proximal
tubule dilatation

11. PATHOGENESIS – POST RENAL AKI
•Increase in intratubular pressures  Abrupt
haemodynamic alterations  An initial period of
hyperaemia from afferent arteriolar dilation 
Intrarenal vasoconstriction (due to generation of
angiotensin II, thromboxane A2, and vasopressin, and a
reduction in NO production).
•Reduced GFR is due to under perfusion of glomeruli
and, possibly, changes in the glomerular ultrafiltration
coefficient.

12. CLINICAL FEATURES
• Urine volume Change : Oliguria, Anuria
• Disturbances of fluid, electrolyte and acid-base balance:
Hyperkalemia, Dilutional hyponatraemia, Metabolic acidosis,
Hypocalcaemia
• Uremic features: pericarditis, neuropathy or decline in mental
status, Coagulopathies with bleeding(epistaxis, GIT,
Intracranial)
• Fluid overload: hypertension, pulmonary edema or heart failure
• Respiratory symptoms: due to metabolic acidosis, pulmonary
oedema

13. HISTORY AND PHYSICAL EXAM
Prerenal azotaemia;
• Should be suspected in the setting of vomiting,
diarrhoea, glycosuria causing polyuria, and several
medications including diuretics, NSAIDs, ACE
inhibitors, and ARBs.
• Physical signs of orthostatic hypotension, tachycardia,
reduced jugular venous pressure, decreased skin
turgor, and dry mucous membranes.

14. HISTORY AND PHYSICAL EXAM
Post Renal
• A history of prostatic disease, nephrolithiasis, or pelvic or
paraaortic malignancy.
• Colicky flank pain radiating to the groin suggests acute
ureteric obstruction.
• Nocturia and urinary frequency or hesitancy can be seen in
prostatic disease.
• Abdominal fullness and suprapubic pain can accompany
massive bladder enlargement.
• Definitive diagnosis of obstruction requires radiologic
investigations.

15. HISTORY AND PHYSICAL EXAM
Intrinsic AKI
• Idiosyncratic reactions to a wide variety of medications can
lead to allergic interstitial nephritis, which may be
accompanied by fever, arthralgias, and a pruritic erythematous
rash.
• AKI accompanied by palpable purpura, pulmonary
haemorrhage, or sinusitis raises the possibility of systemic
vasculitis with glomerulonephritis.
• A tense abdomen should prompt consideration of acute
abdominal compartment syndrome, which requires
measurement of bladder pressure. Signs of limb ischemia may
be clues to the diagnosis of rhabdomyolysis.

16. LABORATORY INVESTIGATIONS
TEST RATIONALE AND INTEPRETATION OF RESULTS
Urea and Creatinine • To assess for severity, stability/progression to CKD
• Prerenal azotaemia  modest rises in SCr that return to baseline with
improvement in hemodynamic status.
• Increases of urea and creatinine concentrations in ATN dependent on
the rate of tissue breakdown in the individual patient.
Electrolytes • Identification of hyperkalaemia, hypophosphatemia, and
hypocalcaemia. and metabolic acidosis; May aid in identifying
aetiology.
• Marked hypophosphatemia w/ accompanying hypocalcaemia, suggests
rhabdomyolysis or the tumour lysis syndrome.
• The anion gap may be increased with any cause of uraemia due to
retention of anions such as phosphate, hippurate, sulphate, and urate.
• Low anion gap may provide a clue to the diagnosis of multiple
myeloma due to the presence of unmeasured cationic proteins.

17. LABORATORY INVESTIGATIONS
TEST RATIONALE AND INTEPRETATION OF RESULTS
Complete Blood Count • Provision of aetiological clues and assessment of severity and progression to
CKD.
• Severe anaemia in the absence of bleeding suggests hemolysis, multiple
myeloma, or thrombotic microangiopathy (e.g., HUS or TTP)
• Other laboratory findings of thrombotic microangiopathy include
thrombocytopenia, schistocytes on peripheral blood smear, elevated lactate
dehydrogenase level, and low haptoglobin content.
• Peripheral eosinophilia can accompany interstitial nephritis, atheroembolic
disease, polyarteritis nodosa, and Churg-Strauss vasculitis.
CRP • Identification of aetiology.
• Elevations indicative of sepsis and inflammatory disease.
Liver Function Tests • Aetiological clues originating from the liver
• Low albumin in nephrotic syndrome
• Low albumin in sepsis: take blood cultures

18. LABORATORY INVESTIGATIONS
• Simple bladder catheterization can R/O urethral obstruction.
• Renal U/S:
• Investigation of obstruction in individuals with AKI unless an
alternate diagnosis is apparent.
• Radiological findings of obstruction include dilation of the
collecting system and hydroureteronephrosis.
• Small kidneys suggest CKD.
• Asymmetric kidneys suggest renovascular or developmental
disease: consider renal artery imaging.
• Kidney biopsy
• Indicated if aetiology not apparent in clinical context.
• Rationale: provision of definitive diagnosis and determination of
prognosis

19. LABORATORY INVESTIGATIONS
• CXR findings:
• Pulmonary oedema in fluid overload
• Globular heart in pericardial (uraemic) effusion: perform
echocardiogram
• ‘Bat wing’ appearance with normal heart size (± low Hb) may suggest
pulmonary haemorrhage: measure CO transfer factor
• Fibrotic change in systemic inflammatory disease with lung and kidney
involvement: request pulmonary function and high-resolution C.
• Laboratory blood tests helpful for the diagnosis of glomerulonephritis and
vasculitis include
• Depressed complement levels
• High titres of antinuclear antibodies (ANAs), antineutrophilic
cytoplasmic antibodies (ANCAs), antiglomerular basement membrane
(AGBM) antibodies, and cryoglobulins.

20. LABORATORY INVESTIGATIONS

21. LABORATORY INVESTIGATIONS

22. DIAGNOSIS
KDIGO criteria
AKI is defined as any of the following (Not
Graded):
•Increase in SCr by X 0.3 mg/dl (X26.5 μmol/l)
within 48 hours; or
•Increase in SCr to X 1.5 times baseline, which is
known or presumed to have occurred within the
prior 7 days; or
•Urine volume 0.5 ml/kg/h for 6 hours.

23. DIAGNOSIS
KDIGO criteria
AKI is defined as any of the following (Not
Graded):
•Increase in SCr by 0.3 mg/dl (26.5 μmol/l)
within 48 hours; or
•Increase in SCr to X 1.5 times baseline, which is
known or presumed to have occurred within the
prior 7 days; or
•Urine volume 0.5 ml/kg/h for 6 hours.

24. DIAGNOSIS
RIFLE Criteria
• Consists of five graded levels of injury: Risk, Injury, Failure, Loss of
function and ESRD;
• Risk: 1.5 fold increase in the SCr or GFR decrease by 25 % or urine
output <0.5 mL/kg per hour for six hours.
• Injury: Two fold increase in SCr or GFR decrease by 50 % or urine
output <0.5 mL/kg per hour for 12 hours.
• Failure: Three fold increase in SCr or GFR decrease by 75 % or urine
output of <0.5 mL/kg per hour for 24 hours or anuria for 12 hours.
• Loss: persistent AKI, or complete loss of kidney function for > 4 wks.
• ESRD: Complete loss of kidney function (e.g. need for RRT) for more
than 3 months.

25. DIAGNOSIS
AKIN Criteria
An abrupt (within 48 hours)onset of:
• An increase in the SCr concentration of ≥ 0.3 mg/dl
(26.4 μmol/L) from baseline, or
• A percentage increase in the SCr concentration of
≥50%
• Oliguria of less than 0.5 ml/kg per hour for more than
six hours

26. RENAL FAILURE INDICES
The fractional excretion of sodium (FeNa)
{
𝑈𝑟𝑖𝑛𝑒 𝑁𝑎+
𝑃𝑙𝑎𝑠𝑚𝑎 𝑁𝑎+
x
𝑃𝑙𝑎𝑠𝑚𝑎 𝐶𝑟𝑒𝑎𝑡𝑖𝑛𝑖𝑛𝑒
𝑈𝑟𝑖𝑛𝑒 𝐶𝑟𝑒𝑎𝑡𝑖𝑛𝑖𝑛𝑒
} x 100
• FeNa <1% = Pre renal AKI (tubules are intact  Na+ reabsorption to maintain
IVV)
• FeNa >2% = ATN (tubular damage tubular Na+ wasting)
• In ischemic AKI, the FeNa is frequently above 1% because of tubular injury and
resultant inability to reabsorb sodium.
• In pre renal azotemia may cause a disproportionate elevation of the
BUN compared to creatinine. Other causes of disproportionate BUN
elevation need to be kept in mind, however, including upper GI
bleeding, hyper alimentation, increased tissue catabolism, and
glucocorticoid use.

27. COMPLICATIONS
• Uraemia which can lead to mental status changes and bleeding complications
• Hypervolemia which leads to weight gain, dependent oedema, increased jugular
venous pressure, and pulmonary oedema.
• Hyponatraemia which, if severe, can cause neurologic abnormalities, including
seizures.
• Hyperkalaemia which results in muscle weakness and potentially fatal
arrhythmias.
• Metabolic acidosis can further complicate acid-base and potassium balance in
individuals with other causes of acidosis, including sepsis, DKA, or respiratory
acidosis.
• Hypocalcaemia can lead to perioral paresthesias, muscle cramps, seizures,
carpopedal spasms, and prolongation of the QT interval on ECG.
• Bleeding, anaemia, infections, malnutrition and cardiac anomalies such as:
arrhythmias, pericarditis and pericardial effusion

28. MANAGEMENT

29. RENAL REPLACEMENT THERAPY
INDICATIONS IN AKI
•Refractory pulmonary oedema
•Persistent hyperkalaemia (K+ >7mmol/L)
•Severe metabolic acidosis (pH<7.2 or base excess <10)
•Uraemic complications such as encephalopathy or
•Uraemic pericarditis (pericardial rub)
•Drug overdose—BLAST: Barbiturates, Lithium, Alcohol
(and ethylene glycol), Salicylates, Theophylline.

30. RENAL REPLACEMENT THERAPY
• The two main options for RRT in AKI are;
• Haemodialysis.
• High-volume hemofiltration, or the hybrid approach of
haemodiafiltration.
• Peritoneal dialysis is also an option if haemodialysis is not
available.
• RRT can be a risky intervention in patients with comorbidity,
since it requires placement of large intravenous catheters that
may become infected and can also represent a major
haemodynamic challenge in unstable patients.

31. PROGNOSIS
• Outcome is usually determined by the severity of the
underlying disorder and other complications, rather than by
renal failure.
• Prerenal azotemia, with the exception of the cardiorenal and
hepatorenal syndromes, and post renal azotemia carry a better
prognosis than most cases of intrinsic AKI.
• In uncomplicated ARF, e.g due to hypovolemia, drugs:
mortality is low
• In ARF associated with Sepsis and MOD, mortality is 50-
70%

32. THANK YOU

33. CHRONIC KIDNEY
DISEASE

34. DEFINITION OF TERMS
• CKD encompasses a spectrum of different pathophysiologic processes
associated with abnormal kidney function and a progressive decline
in GFR.
• Chronic renal failure applies to the process of continuing significant
irreversible reduction in nephron number and typically corresponds
to CKD stages 3–5.
• End-stage renal disease represents a stage of CKD where the
accumulation of toxins, fluid, and electrolytes normally excreted by
the kidneys results in the uremic syndrome .

36. AETIOLOGY

37. RISK FACTORS
• Hypertension
• Diabetes mellitus
• Autoimmune disease
• Older age
• African ancestry
• Family history of renal disease
• Previous episode of acute kidney injury
• Presence of proteinuria,
• Abnormal urinary sediment
• Structural abnormalities of the urinary tract

38. PATHOGENESIS
• Involves two broad sets of mechanisms of damage:
• Mechanisms specific to the underlying aetiology
• A set of progressive mechanisms, involving hyper filtration and
hypertrophy of the remaining viable nephrons, irrespective of
underlying aetiology.
• Reduced nephron numbers  Activation of cytokines and growth
factors  Short-term adaptations of hypertrophy and hyper filtration of
remaining viable nephrons  Further increased pressure and flow
Failure of adaptive mechanisms  Distortion of glomerular
architecture by sclerosis and dropout of the remaining nephrons.

40. CLINICAL SIGNS AND SYMPTOMS
•In majority of patients, CKD is asymptomatic
until GFR falls below 30 ml/min/1.73 m2 (stage 4
or 5).
•Symptoms and signs may develop in almost
every body system in what constitutes the uremic
syndrome (when the serum urea concentration
exceeds 40 mmol/L, but many patients develop
uraemic symptoms at lower levels of serum
urea.).

41. CLINICAL SIGNS AND SYMPTOMS

42. HISTORY AND PHYSICAL EXAMINATION
• History:
• Duration of symptoms
• Drug ingestion, including NSAIDs , analgesic and other
medications, and unorthodox treatments such as herbal
remedies
• Prior exposure to medical imaging radio contrast agents.
• Previous chemotherapy, multisystem diseases such as SLE,
malaria, DM, HTN
• Family history of renal disease.
• Previous measurements of SCr concentration so as to
distinguish newly diagnosed CKD from acute or sub acute
renal failure.

43. HISTORY AND PHYSICAL EXAMINATION
Physical Examination
Periphery: HTN, AV fistula (thrill, bruit, has it been recently needled?), signs of
previous transplant—bruising from steroids, skin malignancy from
immunosuppression.
Face: Pallor of anaemia, yellow tinge of uraemia, gum hypertrophy from
cyclosporin, cushingoid appearance from steroids.
Neck: Current or previous tunnelled line insertion (if removed, look for a small scar
over internal jugular, and a larger scar in ‘breast pocket’ area from the exit site),
scar from parathyroidectomy.
Abdomen: PD catheter or sign of previous catheter (small midline scar just below
umbilicus and small round scar to side of midline from exit site), signs of previous
transplant (hockey-stick scar, palpable mass), ballotable polycystic kidneys ± liver.
Elsewhere: Signs of diabetic neuropathy, retinopathy, cardiovascular or peripheral
vascular disease.

45. LABORATORY INVESTIGATIONS
TEST RATIONALE AND INTERPRETATION OF RESULTS
Urea & Creatinine • Calculation of estimated GFR which is used in assessing
severity
• Comparison with previous results helps in distinguishing
newly diagnosed CKD and acute or sub acute renal failure
Urinalysis and
quantification
of proteinuria
• Haematuria and proteinuria may indicate cause. Proteinuria
indicates risk of progressive CKD and indication for
preventive therapy with ACE inhibitors or ARBs.
Electrolytes • To identify hyperkalaemia and acidosis
Calcium, phosphate,
parathyroid hormone
and
25(OH)D
• Assessment of renal osteodystrophy

46. LABORATORY INVESTIGATIONS

47. COMPLICATIONS
Renal osteodystrophy
• Hyperphosphataemia (due to reduced excretions) and hypocalcaemia (due to reduced
secretions of 1,25 DHCC and consequent reduced gut absorption of Ca2+)  Elevated
PTH  Bone demineralization, osteomalacia, cyst formation and bone marrow fibrosis
(osteitis fibrosa cystica). Elevated Ca2+  Tissue calcifications
Anaemia is due to
• Erythropoietin deficiency (the most significant)
• Bone marrow toxins retained in renal failure
• Bone marrow fibrosis secondary to hyperparathyroidism
• haematinic deficiency – iron, vitamin B12, folate
• Increased haemolysis
• Increased blood loss – occult gastrointestinal bleeding, blood sampling, blood loss
during haemodialysis or because of platelet dysfunction
• ACE inhibitors (may cause anaemia in CKD, probably by interfering with the control of
endogenous erythropoietin

48. Metabolic acidosis
• Reduced renal excretion of H+
CVS anomalies:
• Sodium/water retention: HTN, LVH, CCF,
• Uremia: Pericarditis,
• K+: Arrhythmias
Respiratory anomalies:
• Uremic pleuritis, effusions, pulmonary oedema,
• Metabolic acidosis: Kussmaul’s breathing
GIT:
Uremia: N/V, bleeding, mucosal ulcerations

49. Nervous system:
• Lethargy, confusion, seizures, headaches, peripheral neuropathy,
myopathies
Reproductive system:
• Amenorrhoea, infertility in women
• Loss of libido, impotence and oligospermia in men
Dermatological anomalies
• Dark/Greyish discolouration of the skin( retention of pigments)
• Pruritus,
• Uremic frost
• Petechiae
• Brittle nails and thin hair

50. MANAGEMENT
Anaemia:
• Iron supplementation: IV iron: 100mg IV During dialysis
• Prior to dialysis: oral iron unless patient has tolerability issues
• Oral folate
• ESA ( erythropoiesis stimulating agents): e.g. EPO erythropoietin at
2000-4000 units weekly S/C till HB is 11g/dl
• NB: Avoid transfusions: leads to production of antibodies, making it
difficult to find a match for the patient for transplant.

51. Calcium and phosphate control and suppression of PTH
• Dietary restrictions of phosphates, and
• Oral calcium carbonate or acetate reduces absorption of
dietary phosphate but is contraindicated where there is
hypercalcemia or hypercalciuria.
• Treatment using gut phosphate binders, nicotinamide,
calcitriol or a vitamin D analogue and calcimimetic agents.
Hyperkalaemia
• Dietary restriction of potassium intake.
• Drugs which cause potassium retention should be stopped.
• Ion exchange resins to remove potassium in the GIT may be
used.

52. Hypertension and Proteinuria

53. Oedema:
• High doses of loop diuretics may be needed (eg furosemide 250mg–
2g/24h ± metolazone 5–10mg/24h PO each morning), and restriction
on fluid and sodium intake.
GAPS TO BE ADRESSED
Management hasn’t been covered conclusively, purpose to exhaust
everything
RRT in CKD
Indications for referral of a CKD patient to a nephrologist

54. THANK YOU