ACUTE KIDNEY INJURY &

CHRONIC KIDNEY DISEASE

Dr. W. T. Njumwa
Internal Medicine
ACUTE KIDNEY INJURY(AKI)
Overview

• Acute kidney injury (AKI) - Sudden decline in renal function over hours or days,
causing an accumulation of nitrogenous products in the blood (azotemia).

• AKI has replaced the term “Acute renal failure”

• AKI affects up to 5–7% of acute care hospital admissions and up to 30% of

admissions to the intensive care unit

• Mortality with severe AKI can be up to 30-40%

• A decline in renal function can lead to dysregulation of fluid balance, acid-base

Overview
 AKI diagnostic features include:

• 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.

CLASSIFICATION OF AKI

Criteria used for AKI classification

 RIFLE: Risk, Injury, Failure, Loss of Kidney Function and End

Stage Renal Disease.

 AKIN: Acute Kidney Injury Network

 KDIGO: Kidney Disease Improving Global Outcome

Definition of AKI

Based on the KDIGO criteria, AKI is defined by one of the

following parameters:

1. Increase in serum creatinine by ≥0.3 mg/dL within 48 hours

2. An increase in serum creatinine to ≥ 1.5 times baseline
within 7 days
3. Urine output < 0.5 mL/kg/hr for six hours
The KDIGO criteria divide AKI into three
stages
Aetiology of AKI

Causes of AKI can be classified as

 1-Pre-renal
 2- Intrinsic
 3- Post-renal
1. Pre-renal AKI
AKI occurring secondary to renal hypoperfusion, due to:
• Volume depletion
― hemorrhage
― dehydration
― GI fluid losses. (vomiting, diarrhea)
― Renal losses (diuretics, polyuria)
• Decreased effective circulatory blood volume
― Decrease cardiac output (CHF, MI, Pulmonary embolus)
― Pulmonary hypertension
― Liver failure, Cirrhosis →Hypoalbuminemia
― Septic Shock →systemic vasodilatation
― Anaphylaxis
• Conditions leading to afferent arteriolar vasoconstriction:
― Hypercalcemia
― Drugs, like ACEIs and NSAIDs→ reduces GFR & worsens AKI.

• These pathophysiologic conditions decreases effective arterial circulating volume resulting in reduced kidney
blood flow
2. Intrinsic renal AKI

• Involve intrinsic renal disease or damage

• categorized according to the location of the pathology:
― Tubulointerstitial
― Glomerular
― Vasculature
2. Intrinsic renal AKI…
• Tubular causes -ATN is the commonest cause of renal cause of AKI
Acute Tubular Necrosis often caused by;
― Nephrotoxic drugs-aminoglycosides, Amphotericin B
― Radiocontrast procedures
― Myoglobinuria
― Crystal damage like uric acid, ethylene glycol
― Multiple Myelomas, paraprotenuria, Hypercalcaemia
― NOTE: All prerenal causes can cause ATN
• Interstitial causes
― Acute interstitial nephritis-Drugs (penicillins,NSAIDs,cephalosporins,diuretics)
― Infiltration by lymphoma
― Infection
― tumor lysis syndrome following chemotherapy
2. Intrinsic renal AKI…

• Glomerular causes
― Autoimmune diseases like SLE
― Primary glomerulonephritis
― Nephritic/nephrotic syndrome)
― Infections
• Vascular
― Vasculitis-Small Vessel disease
― Malignant HTN
― HUS/TTP
― microangiopathic haemolytic anaemias, DIC
― Large vessel occlusion-renal artery stenosis and renal artery thrombosis
3. Post-renal AKI
 Due to obstruction of urinary outflow (obstructive uropathy)along the urinary tract from
renal pelvis to urethra.

• Bladder outlet obstruction

― Benign prostatic hypertrophy
― Prostate cancer
― Neurogenic bladder
― Stone disease, hemorrhage/clot
• Ureteral obstruction
― urinary stones (urolithiasis)
― Malignancy ( intraluminal, intramural and extramural tumours)
― Fibrosis,
― Ligation during pelvic surgery
• Urethral obstruction (strictures, tumor)
― Postrenal AKI accounts for less than 10% of cases of AKI
―
Summary of etiology cont’d
Pathophysiology
In all cases of AKI,
• Creatinine and urea build up in the blood over several days
• Fluid and electrolyte disorders develop.
• The most serious of these disorders are hyperkalemia and fluid
overload (possibly causing pulmonary edema).
• Phosphate retention leads to hyperphosphatemia.
• Acidosis develops because hydrogen ions cannot be excreted.
• With significant uremia, coagulation may be impaired, and pericarditis
may develop.
• Urine output varies with the type and cause of AKI.
Evaluation of Acute Kidney Injury

• History taking and physical examinations

• Evaluation of laboratory test results
• Renal imaging
• When appropriate, renal biopsy
 Clinical features-1
1. Symptoms of the underlying primary disease causing AKI
2. symptoms resulting from loss of kidney function
• Urine output:
― oliguria typically from Prerenal causes,
― Anuria usually occurs in obstructive uropathy or, less commonly, in
bilateral renal artery occlusion.
• Urine may be cola-colored in glomerulonephritis or
myoglobinuria.
• Peripheral edema
• Orthostatic hypotension
• Tachycardia
Clinical features-2

• Fluid accumulation in the lungs may cause dyspnea and

crackles on auscultation
• Hemoptysis suggests Goodpasture's syndrome
• A palpable bladder may be present with outlet obstruction.
Clinical features-3

Uremic symptoms
• Anorexia, nausea and vomiting,
• Weakness
• Seizures
• Confusion
• Coma
• hyperreflexia may be present on examination.
• Chest pain (typically worse with inspiration or when
recumbent),
• A pericardial friction rub
Laboratory Tests

• Blood
― Serum creatinine
― Urea and electrolytes
― CRP,ESR,FBC
― Serology: ANA,ANCA, Anti DNA, Anti GBM,

• Urine Assessment
― Leucocytes +nitrites suggests UTI
― Blood and proteins suggests glomerular disease
― RBC casts indicate glomerulonephritis or vasculitis.
― Urinary eosinophils suggest allergic tubulointerstitial nephritis
― Urinary biomarkers for AKI
Diagnosis

• Elevated Serum creatinine

• Elevated BUN concentration (normal range 2.9-8.9 mmol/L])
• Decreased Creatinine Clearance (normal 90–120 mL/min)
• BUN: creatinine ratio
― greater than 20:1 in Prerenal AKI
― Less than 20:1 in intrinsic or Postrenal AKI
 Urinary biomarkers of AKI
• Early biomarkers of AKI:
― Cystatin C
― NAG-N-acetyl beta Glucosaminidase

― NGAL - Neutrophil Gelatinase

Associated Lipocalin
― KIM1- Kidney Injury Molecule 1

― B2M - Beta2 Microglobulin

• Late Biomarkers of AKI

― ↑Serrum Creatinine
― ↑BUN
Imaging in AKI

• Renal ultrasound scan can detect the following

― Obstruction
― Hydronephrosis
― Cysts
― Masses
― Kidney size

― Corticomedullary differentiation

• CT KUB- for masses,urolithiasis,calculi.

• Renal MRI to evaluate masses.
Management of AKI
 Goals of treatment:
• Minimize the degree of kidney insult
• Reduce extrarenal complications
• Restoration of renal function to pre AKI is the ultimate goal

Currently, there is no definitive therapy for AKI, supportive care

is the mainstay of management regardless of etiology
General Principles of management

• Maintenance of adequate cardiac output and blood pressure

to optimize tissue perfusion
• Maintain mean arterial pressure (MAP > 60 mmHg)
• Treatment of underlying infections
• Manage the complications
General Principles of management
• Treatment of underlying etiology
• Restore the volume, match input and output (note insensitive loss =
500mls or more). Avoid fluids containing potassium
• Stop nephrotoxic drugs-(e.g. ACEi, NSAIDs, )
• Daily U&E,
• Track daily weights, BP and Inputs/outputs.
• Fluid management
• Adequate nutrition
• Correction of any hematologic abnormalities
• Dose medications to renal function based on an estimate of the
patient’s GFR.
Complications

• Volume overload
• Electrolyte imbalance
― Hyperkalaemia,
― Hyperphosphatemia
― Hypocalcemia

• Uraemia-pericarditis ,uremic gastritis, encephalopathy.

• Metabolic acidosis PH<7.1
Management of volume overload

• Salt & water restriction

• Loop Diuretics
― effective in reducing fluid overload
― Start IV furosemide 40-80mg and titrate upwards to asses

responsiveness
― thiazide can be added to augment the diuresis

• Pulmonary edema is treated with O2, IV vasodilators (eg,

nitroglycerin), and diuretics
Management of Hyperkalemia
• common life threatening complication of AKI
• ECG→→Tall peaked T wave
Management of metabolic acidosis
• The excretion of acid and regeneration of bicarbonate is impaired
in↓ (GFR) resulting to metabolic acidosis.

• Causes of acidosis are

― Sepsis, trauma, multi organ failure
― Loss of bicarbonate in diarrhea, renal tubular necrosis

• Rx:
― Bicarbonate - NaHCO3
 Indications for dialysis in AKI
General indications for dialysis: AEIOU still stand true to
date.

• Acidosis
― metabolic acidosis refractory to medical management
• Electrolyte Imbalance
― hyperkalemia refractory to treatment K+ > 6 mmol/L
• Intoxicants
― salicylates, lithium, methanol, and ethylene glycol
• Overload of fluid
― volume overload that does not respond to diuresis
― i.e Pulmonary edema persists despite drug treatment
• Uremia
― elevated BUN with signs of uremia, such as uremic bleeding,
encephalopathy, and pericarditis
Prognosis of AKI

• Depends on the severity of underlying illness

• At risk for CKD with repeated AKI episodes.

• May take up to 3 months for patients to recover especially if

they are become dialysis dependent from an acute insult.

• Mortality of > 50% in patients with AKI and multi-organ

dysfunction
CHRONIC KIDNEY DISEASE
(CKD)
Overview

• CKD is progressive disease with high morbidity and mortality

• Commonly associated with uncontrolled diabetes melitus and

hypertension

• As CKD progresses towards end-stage renal disease (ESRD) it

is associated with more symptoms, increasing complications,
and the need for renal replacement therapy (RRT).
Definition criteria for CKD

• Chronic kidney disease (CKD) is defined by the presence of

kidney damage or reduced kidney function for three or
more months.

 Criteria
• Duration ≥3 months, based on documentation or inference
• Glomerular filtration rate (GFR) <60 mL/min/1.73 m2
• Evidence of Kidney damage, as defined by structural or
functional abnormalities other than decreased GFR.
Epidemiology of CKD
• Estimated, 698 million recorded cases of CKD with global
prevalence in the adult population of 13.4% (GBD study 2017)

• Africa-overall CKD prevalence is 15.8% (Kaze AD et al 2018).

• Uganda- estimated CKD prevalence was 6.8% (Anthony N.Muiru

2020).

• Risk factors associated with CKD prevalence in Uganda included age

≥60 years, HIV, diabetes, or hypertension (Anthony N.Muiru 2020).
Markers of kidney damage:

• Albuminuria (Albumin: Creatinine[ACR] ratio > 3 mg/mmol

• Urinary sediment abnormalities (white cell or red cell casts)
• Radiological abnormalities (e.g. polycystic kidneys)
• Pathological abnormalities (e.g. seen on renal biopsy)
• History of kidney transplantation
eGFR & Albumin:Creatinine[ACR] ratio
 eGFR and ACR are two of the key measures in defining CKD

• Formulas to estimate the glomerular filtration rate (eGFR) include:

•Serum creatinine-based calculation
―eGFR = [(140 - age) × Wt / (0.814 × S.Cr in µmol/L)] × (0.85 if female)
•MDRD formula
―186 × [serum creatinine (mg/dl)]−1.154 × (age)−0.203 × (0.742 if female)
•Revised Schwartz formula
―eGFR (ml/min/1.73 m 2 ) = k × height (cm)/serum creatinine (μmol/l) with a k value of 33
•CKD-EPI equation→→precise commonly used
―eGFR = 141 × (min(sCr/κ, 1)α × max(sCr/κ, 1)−1.209 × 0.993age) × 1.018 (if female) ×
1.159 (if Black), where κ is 0.7 for females and 0.9 for males, α is −0.329 for females and
−0.411 for males
• Cystatin C based eGFR
Stages of CKD based on eGFR

• Stage 1: Normal (GFR > 90 mL/min)

• Stage 2: Mild CKD (GFR = 60-89 mL/min)
• Stage 3A: Moderate CKD (GFR = 45-59 mL/min)
• Stage 3B: Moderate CKD (GFR = 30-44 mL/min)
• Stage 4: Severe CKD (GFR = 15-29 mL/min)
• Stage 5: End Stage CKD (GFR <15 mL/min)
Classification of CKD using-eGFR and ACR-

CKD is classified by GFR category (G1–G5),

ACR(Albuminuria) category (A1–A3).

• GFR categories • A1: ACR <3

• G1: 90 or higher • A2: ACR 3-30
• G2: 60–89 • A3: ACR >30
• G3a: 45–59

• G3b: 30–44

• G4: 15–29

• G5: <15
• ACR category
NICE-KDIGO-Classification-of-CKD-using-
eGFR-and-ACR-
Aetiology of CKD

• DM→ Diabetic Nephropathy-common cause

• HTN→ Hypertensive nephropathy

• Glomerulonephritis

• Polycystic Kidney Diseases

• Drugs→acute interstitial nephritis:NSAIDs, sulfa, allopurinol

• Acute kidney injury

• Vascular disease →Renal artery stenosis, Hypertensive nephrosclerosis

• Connective tissue diseases→SLE, Goodpasture syndrome

• Obstructive uropathy→ Urolithiasis, benign prostatic hypertrophy, tumors, urethral
Clinical features
• Asymptomatic in early stages
• Patients develop symptoms at advanced stages (eGFR < 45ml/min).
• Anorexia, Nausea, vomiting, weight loss
• Fatigue & weakness
• Dyspnea
• Pruritus-prominent feature of chronic uremia
• Skin pigmentation-yellow-brown.
• Hypertension is present in > 80%
• Anaemia- pallor, lethargy, breathlessness
• Fluid overload (peripheral & pulmonary oedema)
Clinical features 2

• Platelet abnormality- epistaxis, bruising

• Endocrine/gonads- amenorrhoea, erectile dysfunction,
infertility
• Pericardial Rub
• CNS- confusion, seizures, coma
• Renal- nocturia, oliguria, salt and water retention oedema
• Renal osteodystrophy- osteomacia, muscle weakness, bone
pain, hyperparathyroidism,
• In advanced CKD→ uremic pericarditis, uremic Gastritis and
bleeding are common
Clinical features 3
Diagnosis: investigations
Blood
• FBC
• U&Es (inc. eGFR)
• serum creatinine
• RFTS, ca2+,phosphate
• PTH
• Autoimmune screen (e.g. ANCA, ANA)
Urine
• Urine dipstick: if proteinuria is found offer uACR and serum creatinine
• Urine microscopy
• ACR (spot test)
• ACR (24-hour collection)
Investigations: Imaging Studies
• Plain abdominal x-ray
― to look for radio-opaque stones or nephrocalcinosis

• Renal ultrasound
― Small echogenic kidneys observed in advanced renal failure.

Except in-Diabetic nephropathy, HIVAN, Polycystic kidney disease,

― Hydronephrosis in advanced obstruction,

• Renal artery Doppler: to check the state of the renal arteries.

• CT Scan: to better define renal masses, cysts, most sensitive for
identifying renal stones.
• Renal biopsy: for definitive diagnosis
The principles of CKD management

• Treat the underlying cause

• Treat associated complications of CKD
• Prevent or slow progression of CKD (renoprotective therapy)
• Doses of all drugs adjusted as needed
• Plan for Renal replacement therapy
Complications of CKD
• Anemia
• Hypertension
• Hyperphosphatemia
• Hypocalcemia
• Hyperkalemia
• Secondary Hyperparathyroidism
• Volume overload
• Metabolic acidosis
• Coagulopathy
• Uremic Syndrome
• Mineral and bone disorders (Renal osteodystrophy)
Treating complications of CKD

1.Anemia - Normocytic normochromic anemia

― in CKD due to: deficiency of erythropoietin observed as early as
stage 3 CKD
― Bleeding secondary to platelet dysfunction (due to uremia).
• Platelets do not degranulate in uremic environment .

Rx
• Erythropoietin 50–150 units/kg per week IV or SC (once,
twice, or three times per week)
― Increase Hb by 1–2 g/dL over 4-week period.
― Target Hb 11–12 g/dL
Treating complications of CKD
2. Hyperphosphatemia- with dietary phosphate binders and dietary phosphate
restriction

Phosphate binders

1) Calcium acetate
― Combines with dietary phosphorus to form insoluble calcium phosphate, which is excreted in feces.
― first initial treatment for hyperphosphatemia.

2) Calcium carbonate (Caltrate, Oystercal)

― Combines with dietary phosphate to form insoluble calcium phosphate, which is excreted in feces.

3) Sevelamer (Renagel)
― Binds dietary phosphate in the intestine, thus inhibiting its absorption.
Treating complications of CKD
3. Hypocalcemia: with calcium supplements +/- calcitriol
― CKD→ failure of the 1 alpha hydroxylation of vitamin D to form 1,25
dihydroxycholecalciferol ( occurs in renal tubule).

― Reduced levels of 1,25 (OH)2 Vitamin→ Reduced absorption of calcium from the
GUT, which is often exacerbated by poor oral intake of calcium in patients with
CKD →HYPOCALCEMIA

Rx
• Calcitriol
― Used to suppress parathyroid hormone production in secondary
hyperparathyroidism
― Treatment of hypocalcemia in CKD by increasing intestinal calcium absorption.
― Dose o.25 microgram/day
Treating complications of CKD
4. Secondary Hyperparathyroidism

• Causes of increased PTH in CKD

― Hypocalcemia
― Impaired 1,25-dihydroxyvitamen D production
― Hyperphosphatemia

Rx
• Doxercalciferol (Hectorol)
― A vitamin D analog (1-alpha-hydroxyergocalciferol) that does not require activation by
the kidneys. Indicated for the treatment of secondary hyperparathyroidism

• Calcitriol
Treating complications of CKD
5.Volume overload with loop diuretics
― Restrict dietary salt
― Iv furosemide 40mg od, and titrate as necessary (max. 250mg daily).
― If poor response, consider thiazide diuretic (metolazone 2.5 – 10mg od)
for synergistic effect.
― Refractory volume overload may signal the need for renal replacement
therapy

6.Metabolic acidosis with oral alkali NaHCO3

― Treat when venous HCO3 – is <21mmol/L.
― Refractory acidosis is an indication for dialysis
Treating complications of CKD

8. Hyperkalaemia

Rx:
― This involves stabilization of myocardium (with calcium gluconate)
― Driving potassium into the intracellular compartment (with

insulin/dextrose)
― Potassium-binding resins (e.g. Patiromer, sodium zirconium

cyclosilicate)
Treating complications of CKD

9. Abnormal bleeding and coagulopathy

Rx:
― Desmopressin,

― cryoprecipitate,

― blood transfusions, as well as EPO.

Treating complications of CKD

10. Uremic syndrome

― Due to Large numbers of toxins that accumulate when GFR declines
― include, nitrogen containing products of metabolism

Rx
• Hemodialysis
• peritoneal dialysis,
• Renal transplantation
Prevent or slow progression of CKD
1. Renoprotective therapy
― Aimed at slowing the progression of CKD, independent of the a etiology
― Entails blood pressure control and reducing proteinuria
― BP target of < 130/80 mmHg aimed for patients with CKD
― ideal blood pressure agent ACE-I or ARB
― These drugs are both antihypertensive and antiproteinuric
― Contraindicated in hyperkalemia

2. Other therapies
― Statin therapy
― Smoking cessation
― Antiplatelets for secondary prevention of CVS disease
― Avoiding Malnutrition
― Sodium and water, k+ restriction
Drug Dose Adjustment

• Common drugs that require revised dosing include

― Penicillins,
― Cephalosporins,
― Aminoglycosides,
― Fluoroquinolones,
― Vancomycin, and digoxin

• Drugs to be avoided entirely in ESRD.

― Nitrofurantoin
― Metformin
Renal replacement therapy
 forms of RRT that are indicated for ESRD include
• Hemodialysis,
• Peritoneal dialysis
• Renal transplant

→Renal transplant is considered the gold-standard for RRT

→Renal transplantation requires the use of long-term
immunosuppressive therapy to stop the recipient's immune
system from ‘attacking’ the donor tissue.
Indications for renal replacement therapy

• Hyperkalemia > 6.5 and rising

• Metabolic acidosis- persistent
• Uraemic Symptoms-Pericarditis, gastritis, bleeding diathesis,
Encephalopathy
• GFR<10
• Intractable volume overload
• Pulmonary oedema
Prognosis
• Progression of CKD is predicted in most cases by the degree of proteinuria

• Patients with nephrotic range proteinuria (> 3 g/24 h or urine

protein/creatinine > 3) usually have a poorer prognosis and progress to
renal failure more rapidly.

• In patients with urine protein < 1.5 g/24 h, progression usually occurs more
slowly.

• Hypertension is associated with more rapid progression as well

• The 5-year survival rate for a patient undergoing chronic dialysis is

References

• Harrisson’s,Manual of Medicine,19th Edition,Mc Graw-Hill

Education:New York,2016
• Merck S. & Dohme C.,MSD Manual,Professional
version,Kenilworth:USA,2017
• Upto date 2024
• Medscape 2024