The document discusses disorders of kidney function, providing information on kidney anatomy, physiology, and common renal diseases. It describes the key components of the nephron including the glomerulus, Bowman's capsule, and renal tubules. Investigations for evaluating kidney function such as urine analysis, blood tests, ultrasound, and biopsy are outlined. Common renal disorders like acute kidney injury, chronic kidney disease, glomerular diseases including nephrotic and nephritic syndromes are mentioned.

1. DISORDERS OF KIDNEY
FUNCTIONS
DR KD DELE
DEPT FAMILY MEDICINE
DORA NGINZA
HOSPITAL

2. INTRODUCTION:
GENERAL
OVERVIEW
Kidney disease / renal disease / nephropathy, is
damage to or disease of a kidney.
Nephritis is an inflammatory kidney disease and has
several types according to the location of the
inflammation.
Nephrosis is non-inflammatory kidney disease.
Nephritis and nephrosis can give rise to nephritic
syndrome and nephrotic syndrome respectively.
Kidney disease may be described as acute
(temporary and reversible), or chronic in which
case there is structural damage.
Kidney failure is known as the end-stage of kidney
disease, where dialysis or a kidney transplant is the
only treatment option.

3. EPIDEMIOLOGY
Estimates of the global burden of disease indicate that diseases
of the kidney and urinary tract account for approximately
830,000 deaths annually.
Kidney diseases CKD rank 17th among causes of disability,
accounting for 18,467,000 disability-adjusted life years annually.
Prevalence is 11-13%
Higher prevalence of kidney diseases are found in some ethnic
groups:
CKD disproportionally affects Africans, African Americans and
Hispanics
Males and females are equally affected by kidney disease in terms
of morbidity and mortality

4. EPIDEMIOLOGY…
Generally speaking, available data underestimate the global
prevalence of kidney disease.
This is because individuals with kidney diseases often suffer from
other comorbidities.
For example, patients with CKD often suffer from diabetes, HIV,
cardiovascular or cerebrovascular disease, their deaths may be
attributed to these comorbid complications, rather than CKD.
Approximately 30 percent of patients with diabetes have diabetic
nephropathy

5. EPIDEMIOLOGY…
Natural history:
Renal diseases progress to a final stage as end stage renal disease
(ESRD)
And as such, function is substituted by renal replacement therapy (RRT)
– haemodialysis, peritoneal dialysis, or transplantation.
Evidence show that more than 1.5 million people worldwide are on RRT,
80 percent of whom live in Japan, Europe, and North America.
But,
The percentage of patients on regular dialysis varies across countries as
a consequence of the capacity of health care systems to provide
treatment.

6. ANATOMY & PHYSIOLOGY

7. ANATOMY
AND
PHYSIOLOGY
The kidneys are paired bean-shaped retroperitoneal
structures.
They are located between the transverse processes
of T12-L3 vertebrae
In adults, each kidney is 11–14 cm in length 5–6 cm in
width and 3–4 cm in depth.
The left kidney is located slightly more superior in
position than the right because of the liver on the
right.
The kidney is made up of three main parts: the
outer cortex, the medulla and the renal pelvis.

8. ANATOMY
AND
PHYSIOLOGY
…
The Nephrons:
The Nephrons are the urine producing functional
structures in the kidney
They span the cortex and the medulla (mainly
medulla)
The renal pelvis collects the urine; then urine is
transported out of the kidneys through the ureters
into the bladder.
Neurovascular supply:
Arterial blood is via the renal arteries – a branch off
the abdominal aorta
Venous blood is via the renal veins to the inferior
vena cava.

9. FUNCTIONS
OF THE
KIDNEYS
Filtration and excretion of metabolic waste
products and toxins (urea & ammonium)
Regulation of electrolytes, fluid, and acid-base
balance
Stimulation of red blood cell production
Regulation of blood pressure via the renin-
angiotensin-aldosterone system, controlling
reabsorption of water and maintaining intravascular
volume
Reabsorb glucose and amino acids
Hormonal functions via erythropoietin, calcitriol,
and vitamin D activation

10. THE NEPHRON

11. THE NEPHRON…

12. THE NEPHRON…
Histologically, the functional renal unit is the nephron.
Each nephron is composed of
 An initial filtering component (the “renal corpuscle”)
 A tubule specialized for reabsorption and secretion
(the “renal tubule”).
 A surrounding network of blood capillaries
The renal corpuscle filters out large solutes from the
blood, delivering water and small solutes to the renal
tubule for modification.

13. THE
NEPHRON
…
The Nephron is comprised of the following:
 The renal corpuscle: Glomerulus and Bowman capsule
 The Renal Tubules:
 Proximal convoluted tubules (PCT, located in the renal
cortex)
 Descending limb of loop of Henle (LOH)
 (Thick) Ascending limbof loop of Henle – (which
resides in the renal medulla)
 Distal convoluted tubule
 Collecting duct (which opens into the renal papilla)

15. THE RENAL CORPUSCLE: GLOMERULUS
AND BOWMAN CAPSULE
Glomerulus The glomerulus is a capillary tuft that receives its blood supply from an
afferent arteriole of the renal circulation.
The glomerular blood pressure provides the driving force for water and
solutes to be filtered out of the blood and into the space made by Bowman's
capsule – by 1ommHg hydrostatic pressure – gradient.
The remainder of the blood not filtered into the glomerulus passes into the
narrower efferent arteriole.
The ultrafiltration rate (glomerular filtration rate; GFR) varies with age and
sex but is approximately 120–130 mL/ min per 1.73 m2 surface area in adults.
Bowman's capsule Bowman's capsule surrounds the glomerulus. Fluids from blood in the
glomerulus are collected in the Bowman's capsule (i.e., glomerular filtrate)
and further processed along the nephron to form urine.

16. RENAL TUBULE (READ-UP!)
Proximal Convoluted Tubules Fluid in the filtrate entering the proximal convoluted tubule is reabsorbed into the peritubular
capillaries, including approximately two-thirds of the filtered salt and water and all filtered
organic solutes (primarily glucose and amino acids).
Loop Of Henle It begins in the cortex, receiving filtrate from the proximal convoluted tubule, extends into the
medulla, and then returns to the cortex to empty into the distal convoluted tubule. Its primary
role is to concentrate the salt in the interstitium (i.e. the tissue surrounding the loop.)
Descending Limb LOH The descending limb is permeable to water but completely impermeable to salt; hence as the
filtrate descends deeper into the hypertonic interstitium of the renal medulla, water flows
freely out of the descending limb by osmosis.
Ascending Limb LOH The ascending limb of Henle's loop is impermeable to water. It actively pumps sodium out of
the filtrate, generating the hypertonic interstitium that drives counter-current exchange. In
passing through the ascending limb, the filtrate grows hypotonic since it has lost much of its
sodium content.
Distal Convoluted Tubule The distal convoluted tubule is not similar to the proximal convoluted tubule in structure and
function. Cells lining the tubule have numerous mitochondria to produce enough energy (ATP)
for active transport to take place. Much of the ion transport taking place in the distal
convoluted tubule is regulated by the endocrine system.

17. THE
NEPHRON…
The main function are:
to regulate water and soluble
by filtering the blood,
reabsorbing what is needed
substances and excreting the rest as urine.
Its functions are regulated by the endocrine
system:
by hormones such as antidiuretic hormone,
aldosterone, and parathyroid hormone.

18. THE
NEPHRON…
Its functions are vital to life
25% of cardiac output (approx. 1300 mL/min) –
passes through its 2 million glomeruli.
eliminate wastes from the body
regulate blood volume and pressure
control levels of electrolytes and metabolites
regulate blood pH, blood pressure
Protein-free and fat-free fluid filter across the glomerular
capillary into Bowman’s capsule into the renal tubule.

19. THE
NEPHRON…
Its functions are vital to life
25% of cardiac output (approx. 1300 mL/min) –
passes through its 2 million glomeruli.
eliminate wastes from the body
regulate blood volume and pressure
control levels of electrolytes and metabolites
regulate blood pH, blood pressure
Protein-free and fat-free fluid filter across the glomerular
capillary into Bowman’s capsule into the renal tubule.

20. GLOMERULAR FUNCTIONS cont.
The GFR is normally constant owing to intrarenal regulatory mechanisms.
In disease, GFR drops – the ability to eliminate waste material and to regulate the
volume and composition of body fluid will decline.
The concentration of urea or creatinine in plasma thus will rise.
(Serum urea and creatinine do not rise above the normal range until there is a
reduction of 50–60% in the GFR.)
However, a normal serum urea or creatinine is not synonymous with a normal GFR.

21. GLOMERULAR FUNCTIONS cont.
UREA
• the level of urea depends both
on the GFR and its production
rate
• Urea production is heavily
influenced by protein intake and
tissue catabolism.
Raised Serum UREA (Source:
Clinical Medicine Kumar&Clarke).
CREATININE
• The level of creatinine is much
less dependent on diet but is
more related to age, sex and
muscle mass.
• Once the serum creatinine is
elevated, it is a better guide to
GFR than urea
• Measurement of serum
creatinine is a good way to
monitor further deterioration in
the GFR.

22. OTHER FUNCTIONS OF THE KIDNEY
Tubular Function
• The active reabsorption from the
glomerular filtrate of
compounds such as glucose and
amino acids
• Acid–base balance
• Protein and polypeptide
metabolism
• Drug and toxicant elimination –
such as penicillins, diuretics,
NSAIDs, cephalosporins,
antivirals and methotrexate
Endocrine Function
• Renin–angiotensin system –
(systemic vasoconstriction and
sodium and water retention)
• Erythropoietin – the major
stimulus for erythropoiesis
• (Loss of renal substance/
decreased EPO production –
normochromic, normocytic
anaemia, increased EPO –
polycythaemia)
• Vitamin D metabolism
Autocrine function
Endothelins
Prostaglandins
Urodilatin: renal natriuretic peptide
Nitric oxide

23. RENAL FUNCTION:
INVESTIGATIONS

24. INVESTIGATIONS: URINE
Proteinuria
• Proteinuria is one of the most
common signs of renal disease
• Normal: <30 mg in 24 hours
• Microalbuminuria if 30–300 mg /
24 hours, and an early indicator
of diabetic glomerular disease
• Most test strips detect protein if
albuminuria exceeds 300 mg/d.
• If proteinuria is confirmed on
repeated dipstix, 24-hour urine
collections to measure the
precise protein excretion
• However, in practice, spot Urine
albumin : creatinine ratio is used
Glucosuria:
• a positive test for glucose in
urine always requires exclusion
of diabetes mellitus
Haematuria
• Haematuria may be overt (with
bloody urine), or microscopic’
• Haematuria on disptix should be
followed by urine microscopy
• If red-cell casts are detected, it
diagnoses glomerulonephritis
• Overt bleeding often signifies a
disease of bladder, urethra or
prostate
• Appearance (rarely)
• Volume (N: 800–2500 mL / 24
hours)
• Specific gravity and osmolality
(rarely, e.g. SIADH)
• Urinary pH (rarely, e.g. in RTA)
Urine dipstix:
• Routine Stix testing of urine for
blood, protein and sugar in all
patients suspected of having
renal disease.
Bacteriuria = UTI
• Based on the detection of nitrite
• +/- leucocyte

25. INVESTIGATIONS: URINE
Casts
• Moulded in the shape of the
distal tubular lumen
• May be hyaline, granular,
cellular
• Coarse granular casts: occur
with pathological proteinuria in
glomerular and tubular disease.
• Red-cell casts: always indicate
renal disease (even if single)
• White cell casts: in acute
pyelonephritis.
• Tubular cell casts: in acute
tubular necrosis.
White blood cells:
• The presence of 10 or more
WBCs per mm3 is abnormal.
• Suggestive of UTI, stones,
tubulointerstitial nephritis,
papillary necrosis, tuberculosis
and interstitial cystitis
Red cells
• The presence of one or more
red cells per mm3 is abnormal
URINE MICROSCOPY
• Urine microscopy should be
carried out in all patients
suspected of having renal
disease
• Use a ‘clean’ sample of mid-
stream urine.
• Alternatively, in suspected
urinary tract infections,
suprapubic aspiration is required
particularly in children

26. INVESTIGATIONS: BLOOD & U/S
ULTRASOUND contd.
• Guide for renal biopsy or other
interventional procedures
• Characterizing renal masses as
cystic or solid
• Diagnosing polycystic kidney
disease.
• Detecting intrarenal and/or
perinephric fluid (e.g. pus,
blood).
• Doppler scan – in renal arterial
perfusion or detecting renal vein
thrombosis
Disadv.:
• It is operator-dependent.
ULTRASOUND
• KUB (Ultrasonography of the
kidneys and bladder)
• Preferred over X-ray & other
radiation techniques
• (avoidance of ionizing radiation
& IV contrast medium.)
USES
• Renal measurement
• Corticomedullary differentiation
(poor)
• pelvicalyceal dilatation as an
indication of renal obstruction/
hydronephrosis
BLOOD
Serum Urea
Serum creatinine
eGFR
Creatinine clearance estimation
___
Others, based on presentation
Complements c3/c4
ANCA in vasculitis
*NB. The kidney is particularly
susceptible to damage by
complement

27. ESTIMATE CREATININE CLEARANCE

28. INVESTIGATIONS: IMAGING
Others include
• Antegrade pyelography
• Retrograde pyelography
• Micturating cystourethrography
• Renal scintigraphy
_____
Renal Biopsy (u/s guided)
Useful in:
• nephritic and nephrotic
syndromes,
• acute and chronic renal failure,
• haematuria after urological
investigations
• renal graft dysfunction
Magnetic resonance imaging
• Magnetic resonance urography
• (preferred over intravenous
urography (IVU))
Excretion urography
• (also known as IVU or
intravenous pyelography (IVP))
• largely been replaced by U/S, CT
& MRI scanning.
Aortography or renal
arteriography
• (‘gold standard’ for renal artery
imaging)
Plain X-ray (Abd X-Ray):
• for renal calcification or radio-
dense calculi in the kidney, renal
pelvis, line of the ureters or
bladder
Computed tomography (CT)
• to characterize renal masses
indeterminate by U/S
• to stage renal/ bladder/ prostate
tumours
• to assess severe renal trauma
• NB>radiation and contrast
nephrotoxicity

29. DISORDERS OF THE
RENAL SYSTEM

30. DISORDERS
OF THE
RENAL
SYSTEM
These conditions include the following:
 Glomerular disease e.g. Nephrotic syndrome,
Nephritic Syndrome
 Acute Kidney Injury (AKI)
 Chronic Kidney Disease (CKD)
 HIVAN
 Renal stones (Nephrolithiasis)
 Polyuria
 Renal acidosis
 UTI

31. GLOMERULAR DISEASE:
NEPHROTIC SYNDROME /
NEPHRITIC SYNDROME

32. GLOMERULAR DISEASE
Glomerulonephritides are a group of kidney diseases that affect the glomeruli.
Structure predisposes it to immune complex deposition and complement fixation
They fall into two major categories:
1. Glomerulonephritis: refers to an inflammation of the glomeruli and can be
primary or secondary
2. Glomerulosclerosis: refers to scarring of the glomeruli.

33. GLOMERULAR
DISEASE…
A number of different diseases can result in
glomerular disease:
It may be the direct result of an infection or a drug
toxic to the kidneys. It may also result from
systemic diseases, like diabetes or lupus.
Even though glomerulonephritis and
glomerulosclerosis have different causes, both can
lead to ESRD.
Glomerulonephritis ranks third after diabetes
mellites and hypertension as the foremost cause
of ESRD in Europe.
Approximately 15 percent of patients
requiring RRT have a glomerular disease.

34. GLOMERULAR
DISEASE…
Glomerular diseases are more prevalent
and severe in tropical regions and low-
income countries
A common mode of presentation is the
nephrotic syndrome, with the peak age of
onset at five to eight years.
A number of kidney diseases can result from infectious
diseases endemic to tropical Africa and low income
countries. These include malaria, schistosomiasis, leprosy,
filariasis, and hepatitis B virus, including HIV/AIDS
Acute poststreptococcal nephritis following a throat or
skin infection caused by Group A streptococcus has
almost disappeared in high-income countries because of
improved hygiene and treatment but remains an
important glomerular disease in India and Africa

35. GLOMERULAR
DISEASE…
The signs and symptoms of glomerular disease
include
 Proteinuria/albuminuria
 Haematuria
 Reduced glomerular filtration rate due to
inefficient filtering of wastes from the blood
 Hypoproteinaemia
 Oedema

36. NEPHROTIC VS NEPHRITIC
DISORDERS
• Profound proteinuria
• Immune complex deposits: Epithelial
• NO cellular inflammatory reaction
Nephrotic:
• Variable proteinuria
• Immune complex deposits: Subendothelial or Glomerular basement
membrane
• Cellular inflammatory reaction
Nephritic:

37. NEPHROTIC SYNDROME

38. NEPHROTIC
SYNDROME
Many diseases and conditions can cause glomerular
damage and lead to nephrotic syndrome, including:
 Diabetic kidney disease.
 Minimal change disease: the commonest
especially in children
 Focal segmental glomerulosclerosis eg HIVAN.
 Membranous nephropathy.
 Systemic lupus erythematosus.
 Amyloidosis.

39. NEPHROTIC
SYNDROME:
SIGNS AND
SYMPTOMS
•an increase in permeability of the capillary walls of the
glomerulus
•leading to the presence of high levels of protein
passing from the blood to the urine.
It is characterized by:
•Proteinuria (nephrotic range >3.5g/day)
•Hypoalbuminemia
•Hyperlipidaemia
•Oedema
•Lipiduria can also occur but is not essential for the
diagnosis of nephrotic syndrome.
•Hyponatremia also occur with a low fractional sodium
excretion.
It is characterized by

40. NEPHROTIC
SYNDROME:
DIAGNOSIS
+ Oedema (from low albumin)
+ nephrotic range proteinuria
± microscopic haematuria
+ without signs of intravascular overload (no
gallop, no creps, no right heart failure signs,
no hypertension).

41. NEPHROTIC SYNDROME:
DIAGNOSIS
Diagnostic:
 Spot urine Prot/Creat ratio
 albumin & protein
 cholesterol.
Causation:
 Hep. B, syphilis, ASOT, anti-DNAse, C3 C4, HIV ELISA +/- malarial smear etc.
Renal function:
 Urea, creatinine and electrolytes.
Others: CXR, GXP, FBC
Protein:Creatinine Ratio (UPCR):
Urinary Protein (g/l) X 1000
Urinary Creatinine (mmol/l)
Normal ≤20mg protein/mmol creatinine.
Nephrotic >200mg protein/mmol creatinine.
(Random early morning urine sample.)

42. NEPHROTIC SYNDROME:
TREATMENT
Corticosteroids
 High dose prednisone: 2mg/kg/dose (max. 80mg/day) oral in the morning
 Urine dipstix every morning to monitor protein.
 Start tapering over next 4 months if no proteinuria for 72 consecutive hours.
Immunosuppressive agents such as Cyclophosphamide and cyclosporine may be
used in steroid resistant nephrotic syndrome to induce remission
Rituximab has been shown to be effective for patients with complicated
frequently relapsing/steroid-dependent nephrotic syndrome.
NB There’s up to 50-85% relapse in NS

43. NEPHROTIC SYNDROME:
TREATMENT
Corticosteroids (high dose prednisone)
Diuretics (Lasix/HCTZ) – may be used to reduce oedema
ACE-inhibitors and Angiotensin II receptor blockers – reduce proteinuria
Low salt diet
Normal to high protein diet
Monitor weight – daily weighing
Pneumococcal vaccine – prophylaxis of secondary infection

44. NEPHROTIC SYNDROME:
COMPLICATIONS
These include:
•Thromboembolism (NS being
hypercoagulable state)
•Infection (increased risk)
•Acute kidney failure
•Pulmonary oedema
•Massive ascites
•Hypocalcaemia
•Microcytic anaemia
•Protein malnutrition
•Growth retardation
•Vitamin D deficiency
•Cushing’s syndrome

45. NEPHROTIC SYNDROME

46. NEPHRITIC SYNDROME
ACUTE GLOMERULONEPHRITIS (AGN)
Most intrinsic causes of acute glomerulonephritis fall under the
classification of nephritic syndrome
Glomerulonephritis or acute nephritic syndrome
• This is a disorder / inflammation of the glomeruli
• It is characterized by:
• Oedema
• High blood pressure
• Haematuria

47. NEPHRITIC SYNDROME/
ACUTE GLOMERULONEPHRITIS (AGN)
Presentation (a combination of):
 Oedema
 Haematuria (painless)
 Hypertension
 Oliguria
 Proteinuria
 Pulmonary oedema.
 Impetigo

48. NEPHRITIC SYNDROME/
ACUTE GLOMERULONEPHRITIS (AGN)
In Paediatrics
1. IgA Nephropathy: Mesangial deposits – autoimmune
2. Post-infectious glomerulonephritis: Subepithelial e.g., Acute post-
streptococcal glomerulonephritis (PSGN)
3. Hemolytic uremic syndrome
In Adults
4. Minimal change disease (MCD)
5. Membranous nephropathy: Subepithelial deposits
6. Lupus glomerulonephritis: Subendothelial deposits
7. Goodpasture’s Syndrome: Antibody binding to GBM – autoimmune
8. Glomerular injury with proteinuria: Podocyte effacement

51. GLOMERULAR
DISEASE:
DIAGNOSIS
•Dipstick, microscopy, culture.
•RBC casts (fresh urine) – diagnostic
Urine:
•Serum albumin; Electrolytes, urea, creatinineASOT /
Strep anti-DNAse), C3 & C4.
•FBC/CRP/ESR to check for systemic causes
Blood:
•Ultrasound (KUB)
Imaging tests -
Kidney biopsy
Chest X-Ray.

52. NEPHROTIC VS NEPHRITIC

53. TREATMENT
Goal of
Treatment:
To relieve symptoms
To prevent complications
To delay kidney damage
Treat underlying cause
Lifestyle modification
The treatment
of glomerular
disease
depends on
the form (whether it is acute or chronic glomerular disease)
the underlying cause
the severity of associated signs and symptoms

54. TREATMENT
Observations: Blood pressure 4 hourly, strict
intake and output, daily weighing, daily dipstick,
daily macroscopic examination of urine.
Observe
Restrict activity until hypertension,
macroscopic haematuria and oedema have
settled.
Restrict
Restrict sodium intake until diuresis and fluid
overload / hypertension have settled. Avoid
added salt, canned meat, peanuts, chips etc.
Restrict
Restrict fluids to insensible losses (10-
25ml/kg/day) until good diuresis occurs with
loss of weight and normal BP / CVS function.
(The smaller figure for bigger children).
Restrict
Restrict protein / potassium intake until urea
<20mmol/l. (Bread & jam diet usually
adequate).
Restrict

55. TREATMENT
• Treat blood pressure that is above the 95th (99th)
percentile for age and gender
• Medications commonly used: ACE-Inhibitors.
ARBs.
• Added advantage of reducing protein lost in
urine.
• If the child has symptomatic hypertension, treat
as a hypertensive emergency – use both diuretic
and antihypertensive agent.
Hypertension:
• Furosemide 1-2(max. 5)mg/kg/dose slow IV.
Congestive fluid overload /
Pulmonary oedema:

56. BLOOD PRESSURE CENTILES

57. TREATMENT
Other modalities as needed:
• Patients may need to be nursed Fowler’s position,
• oxygen,
• morphine sedation,
• Intermittent Positive Pressure Ventilation,
• dialysis.
Antibiotics (penicillins) for 10 days (esp if
Acute Post-Streptococcal
Glomerulonephritis (APSGN) is suspected)
Antiseptic ointment and washes to treat
impetigo

58. PROGNOSIS
Because nephritic syndrome is not a disease, the prognosis depends on
the underlying cause.

59. ACUTE KIDNEY
INJURY

60. ACUTE
KIDNEY
INJURY
Acute kidney injury is a medical emergency!
It is characterised by a sudden, rapid (hours to
days), and usually temporary loss of kidney
function
The decline in kidney function is measured by
fall in glomerular filtration rate.
It may be so severe that renal replacement
therapy is needed until kidney function
recovers.
Even though acute renal failure can be a
reversible condition, it carries a high mortality
rate.

61. INTRODUCTION: AKI
Retention of nitrogenous waste products, oliguria (urine output <400 mL/d),
and electrolyte and acid-base abnormalities are frequent clinical features
Others include haematuria, proteinuria, edema, hyper/hypotension
AKI is usually asymptomatic
It is usually diagnosed when biochemical monitoring of hospitalised patients
reveals a new increase in blood urea and serum creatinine concentrations.
Most people who experience acute kidney injury have some degree of pre-
existing chronic kidney disease

62. RISK FACTORS
The prevalence of acute kidney injury (and CKD) increases with age
The incidence of severe AKI is more than fifty times higher in people aged over 80 years than in
people aged under 50 years.
Diabetes mellitus, hypertension, obesity and proteinuria are independent risk factors for AKI.
People with co-existing diabetes mellitus and CKD are at even greater risk of developing AKI.
Older people, and people have poor mobility and reduced access to fluids when unwell, have an
increased risk of pre-renal injury.
Polypharmacy, including nephrotoxic medicines increases the likelihood of an AKI or acute-on-
chronic decline in renal function.

63. CAUSES OF
ACUTE
KIDNEY
INJURY
(AKI)
Three major categories:
A. Prerenal AKI: diseases that cause renal hypoperfusion,
resulting in decreased function without frank
parenchymal damage
B. Intrinsic AKI: diseases that directly involve the renal
parenchyma
C. Post-renal AKI: diseases associated with urinary tract
obstruction

65. A. PRERENAL AKI
A reduction in blood flow to the kidney is the most common cause of acute kidney
injury.
The resulting renal injury is due to the inability to maintain renal blood flow via
autoregulation and is not due to direct damage to the nephron itself.
The defining feature of acute pre-renal injury is that if normal blood flow can be re-
established, renal function will often rapidly recover.
However, a sustained reduction in renal perfusion increases the risk of intrinsic renal
injury (acute tubular necrosis), which may result in irreversible damage to the kidney.

66. AKI: PRE-RENAL CAUSES
Hypovolemia
•Increased extracellular fluid losses: haemorrhage
•Gastrointestinal fluid loss: vomiting, diarrhoea,
enterocutaneous fistula
•Renal fluid loss: diuretics, osmotic diuresis, hypoadrenalism
•Extravascular sequestration: burns, pancreatitis, severe
hypoalbuminemia (hypoproteinaemia)
•Decreased intake: dehydration, altered mental status

67. AKI: PRE-RENAL CAUSES
Altered Renal Haemodynamic Resulting In Hypoperfusion
Low cardiac output state:
• diseases of the myocardium, valves, and pericardium (including tamponade);
• pulmonary hypertension or massive pulmonary embolism;
• impaired venous return
Systemic vasodilation:
• sepsis, antihypertensives, afterload reducers, anaphylaxis

68. AKI: PRE-RENAL CAUSES
Altered Renal Haemodynamic Resulting In Hypoperfusion
Renal vasoconstriction:
• hypercalcemia, catecholamines, calcineurin inhibitors/cyclosporine , amphotericin B
Impairment of renal auto-regulatory responses:
• cyclooxygenase inhibitors (NSAIDS)
• angiotensin-converting enzyme inhibitors (ACE-I)
• angiotensin II receptor blockers (ARBs)
Hepato-renal syndrome

69. Three-year Outcomes After Acute Kidney Injury: Results Of A
Prospective Parallel Group Cohort Study
Kerry L Horne1, Rebecca Packington1, John Monaghan2,
Timothy Reilly3, Nicholas M Selby. BMJ Open 2017;7:e015316.
Doi:10.1136/Bmjopen-2016-015316

70. CLINICAL
ASSESSMENT:
PRE-RENAL
AKI
• asymptomatic, thirst and orthostatic dizziness
Symptoms:
• Orthostatic hypotension, Tachycardia, Reduced
jugular venous pressure, Decreased skin turgor
and Dry mucous membranes
Physical signs:
• may reveal stigmata of chronic liver disease and
portal hypertension, advanced cardiac failure,
sepsis, or other causes of reduced "effective"
arterial blood volume
Careful clinical examination

71. B. AKI: INTRINSIC RENAL CAUSES
Intrinsic renal injury is characterised by direct damage to the nephrons.
It is often complex and may be secondary to another illness.
The most common cause of intrinsic injury is acute tubular necrosis as a result of
pre-renal injury or direct toxicity (hypotension, hypovolaemia, haemolysis,
rhabdomyolysis or nephrotoxic medicines, e.g., NSAIDs, lithium or
aminoglycosides).
The combination of pre-renal injury and acute tubular necrosis accounts for
approximately 90% of cases of acute kidney injury.

72. Renovascular obstruction
Diseases of the glomeruli or vasculature
Acute tubular necrosis
Intratubular obstruction
Interstitial nephritis

73. B. AKI: INTRINSIC RENAL CAUSES
1. Renovascular obstruction
This may be bilateral, or unilateral in the setting of one kidney
Renal artery obstruction:
•Atherosclerotic plaque
•Thrombosis / embolism
•Dissection aneurysm
•Large vessel vasculitis
Renal vein obstruction:
•Thrombosis or compression

74. B. AKI: INTRINSIC RENAL CAUSES
2. Diseases of the glomeruli or vasculature
Glomerulonephritis or vasculitis
Others:
•Thrombotic microangiopathy
•Malignant hypertension
•Collagen vascular diseases (SLE, scleroderma)
•DIC
•Preeclampsia / Eclampsia / PET

75. B. AKI: INTRINSIC RENAL CAUSES
3. Acute tubular necrosis
Ischemia:
• causes same as for prerenal AKI, but generally the insult is more severe and/or more
prolonged
Infection, with or without sepsis syndrome
Toxins:
• Exogenous (radiocontrast, antibiotics ,chemotherapy) Endogenous
(rhabdomyolysis, haemolysis )

76. B. AKI: INTRINSIC RENAL CAUSES
4. Intratubular obstruction
Endogenous:
•myeloma proteins, uric acid (tumour lysis syndrome), systemic oxalosis
Exogenous:
•acyclovir, ganciclovir, methotrexate, indinavir

77. B. AKI: INTRINSIC RENAL CAUSES
5. Interstitial nephritis
•Drugs: antibiotics (B-lactams, sulphonamides, quinolones, rifampin),
NSAIDS, diuretics, other drugs
•Infection: pyelonephritis (if bilateral)
•Infiltration: lymphoma, leukaemia, sarcoidosis
•Inflammatory: Sjögren's syndrome, tubulo-interstitial nephritis with
uveitis

78. CLINICAL ASSESSMENT:
Diseases of small vessels and glomeruli
•Glomerulonephritis/vasculitis :
•New cardiac murmur (post-infectious IE)
•Skin rash/ulcers, arthralgias (lupus)
•Sinusitis (anti-GBM disease)
•Lung haemorrhage (anti-GBM, ANCA, lupus)
•Malignant hypertension

79. CLINICAL ASSESSMENT:
Diseases of small vessels and glomeruli (cont.)
•Haemolytic-uremic syndrome/thrombotic thrombocytopenic:
•Fever, neurologic abnormalities
•Evidence of damage to other organs:
•headache
•papilloedema
•heart failure with LVH by echocardiography/ECG (Typically resolves
with blood pressure control)

80. CLINICAL ASSESSMENT:
Diseases of large renal vessels
•Renal artery thrombosis:
•Flank or abdominal pain
•Athero-embloic disease:
•Retinal plaques, palpable purpura, livedo reticularis
•Renal vein thrombosis:
•Flank pain

81. C. POST-RENAL/ UT
OBSTRUCTION
These are mostly urinary tract obstruction
Ureteric
•They may be bilateral, or unilateral in the case of one kidney
•They include calculi, blood clots, sloughed papillae, cancer, external compression (e.g..
retroperitoneal fibrosis)
Bladder neck:
•neurogenic bladder, prostatic hypertrophy, calculi, blood clots, cancer
Urethra:
•stricture or congenital valves
The site, degree and speed of onset of the obstruction determine the clinical symptoms and signs.

82. POST-RENAL
AKI:
CLINICAL
ASSESSMENT
History of renal stones or
prostatic disease
Palpable bladder, flank or
abdominal pain
Imaging to
assess obstruction:
CT scan
and/or
ultrasound

83. AKI: WORKUP
Several laboratory tests, including the following, are:
useful for assessing the aetiology of acute kidney injury
•Full blood count (FBC)
•Serum biochemistries
•Urine analysis with urine microscopy
•Urine electrolytes
•Creatinine clearance (Cr Cl)
and can aid in proper management of the disease:

84. MANAGING ACUTE KIDNEY
INJURY
Acute kidney injury should be considered a medical emergency.
If there is a clearly identifiable cause, then this should be managed.
If the cause of deterioration is not clear, consider discussion with renal unit.
If a patient is found to have an elevated serum creatinine level during routine
monitoring, or following investigation of a concurrent illness:
the first step is to determine whether the decline in renal function is due to CKD
or acute kidney injury – as the management of the two conditions varies.

85. MANAGING ACUTE KIDNEY
INJURY
Previous creatinine measurements are the most useful tool for confirming and
assessing the severity of acute kidney injury.
Patients who have a single raised serum creatinine and no baseline serum
creatinine measurements should be assumed to have acute kidney injury.
Red flags requiring urgent hospital admission / referral include:
• Negligible urine output for 6 hours or < 200 mL over 12 hours
• Serum potassium > 7.0 mmol/L or > 5.5 mmol/L with ECG changes
• Volume overload
• Creatinine concentration > 300 μmol/L or a change of 50%

86. HISTORY
Key points within the history include:
 Any recent acute illness
 Symptoms suggestive of outflow obstruction such
as prostate symptoms or abdominal pain in acute
obstruction
 A history of abdominal or pelvic malignancy
causing obstruction or myeloma causing intrinsic
injury from heavy proteinuria
 Systemic symptoms, such as a rash, joint or
muscle pain suggesting an underlying systemic
disease or vasculitis
 Current medications
 Recent contrast radiology
 Pre-existing conditions or a family history of renal
disease

87. EXAMINATION
Physical examination
Assess whether the patient is
1. dehydrated (e.g., thirst, dry mucous membranes,
reduced urinary output, tachycardia) or
2. fluid overloaded (e.g., raised jugular venous
pressure, features of pulmonary and peripheral
oedema).
Look for features of systemic disease, such as
fever, skin rashes, joint swelling, iritis or peripheral
vascular disease.
The abdomen should be examined for masses,
organomegaly, abdominal aortic aneurysm and the
bladder palpated and percussed for possible
outflow obstruction

88. MANAGING
ACUTE
KIDNEY
INJURY
The focus of management of acute kidney injury is to:
1. Restore renal blood flow
2. Treat urinary obstructions
3. Review medicine use

89. MANAGING
ACUTE
KIDNEY
INJURY
Restoring renal blood flow
Restoration of renal perfusion is the goal in the
treatment of pre-renal causes of acute kidney injury.
Fluid replacement is the simplest way of achieving
this.
However, post-renal obstruction first needs to be
excluded.
Also caution with fluid overload
Treatment should also target the underlying cause for
the volume loss, e.g., diarrhoea or vomiting.

90. MANAGING
ACUTE
KIDNEY
INJURY
Treating urinary obstructions
Obstruction relief is the goal of treatment in patients
with post-renal acute kidney injury.
This is necessary to prevent irreversible kidney
damage and for patient comfort.
A urethral or suprapubic catheter will relieve
obstructions located at the level of the urethra or
bladder, respectively.
If an obstruction of the urinary tract is suspected,
then the patient should be referred to an urologist.

91. MANAGING
ACUTE
KIDNEY
INJURY
Medicine review
Patients with acute kidney injury should
discontinue nonessential, nephrotoxic medicines,
e.g. NSAIDs.
Patients with dehydration and pre-renal injury
should have their ACE inhibitors, ARBs or diuretics
withheld until renal function has recovered.
A complete medicine review should also be
undertaken either in primary or secondary care as
appropriate.

92. DIALYSIS
Consider need for dialysis if:
1. Blood urea >45-50mmol/l (creatinine >1000-
1500mcmol/l).
2. Medically uncontrollable hyperkalaemia.
3. Medically uncontrolled acidosis
4. Life threatening fluid overload not
responding to diuretics.
5. Clinical uraemic syndrome (decreased LOC /
convulsions).

93. AKI:
COMPLICATIONS
Metabolic acidosis
hyperkalaemia
pulmonary oedema
 may require medical treatment with sodium
bicarbonate, shifting potassium, and diuretics
Lack of improvement with fluid resuscitation
therapy-resistant hyperkalaemia
metabolic acidosis
fluid overload
 (may necessitate artificial support in the form of
dialysis or hemofiltration)

94. CHRONIC KIDNEY
DISEASE

95. INTRODUCTION – CKD
Chronic kidney disease (CKD) encompasses a spectrum of different
pathophysiologic processes associated with abnormal kidney function, and a
progressive decline in glomerular filtration rate (GFR).
CKD may be defined as Kidney damage for > 3 months, defined by structural or
functional abnormalities of the kidney, with or without decreased GFR.
Two Screening Tests
eGFR
ACR (Albumin/Creatinine ratio) (spot UPCR)

96. INTRODUCTION – CKD
Chronic kidney disease is a worldwide threat to public health
But the size of the problem is probably not fully appreciated.
Estimates of the global burden of the diseases report that diseases of the kidney and urinary tract
contribute with ∼830 000 deaths annually and 18 867 000 disability-adjusted life years (DALY)
Thus, CKD ranks as the 12th highest cause of death (1.4% of all deaths) and the 17th cause
of disability (1% of all DALY).
Chronic kidney disease is a key determinant of the poor health outcomes for major NCDs
– cardiovascular diseases, diabetes mellitus, cancers, and chronic lung disease

97. Nephrology Dialysis Transplantation, Volume 27, Issue suppl_3, October 2012, Pages iii19–iii26, https://doi.org/10.1093/ndt/gfs284
The content of this slide may be subject to copyright: please see the slide notes for details.
FIG. 1. PREVALENCE OF ESRD (DIALYSIS AND
TRANSPLANTATION) WORLDWIDE. DATA ARE FROM THE
2011 USRDS ANNUAL REPORT AND ...
• Overall there are
∼1.8 million people
in the world who are
alive simply because
they have access to
one form or another
of RRT
• Patients on RRT can
be regarded as the
tip of the iceberg
• whereas the number
of those with CKD
not yet in need of
RRT is much greater

98. CKD: RISK FACTORS

100. CKD: CAUSES
The three most common causes of CKD are
1. diabetes mellitus
2. Hypertension
3. Glomerulonephritis
Together, these cause approximately 75% of all adult cases.

101. CKD:
CAUSES
•Large vessel disease such as bilateral renal
artery stenosis
•Small vessel disease such as ischemic
nephropathy, haemolytic-uremic syndrome,
and vasculitis.
Vascular disease
Glomerular disease
•Primary glomerular disease such as focal
segmental glomerulosclerosis e.g., in
HIV and IgA nephropathy (or nephritis)
•Secondary glomerular disease such as diabetic
nephropathy and lupus nephritis
Comprises a diverse group and is
classified into:

102. CKD:
CAUSES
• Such as polycystic kidney disease.
Congenital disease
• Includes drug- and toxin-induced chronic
tubulointerstitial nephritis, and reflux
nephropathy.
Tubulointerstitial disease
• bilateral kidney stones and
• diseases of the prostate such as benign
prostatic hyperplasia.
Obstructive nephropathy

103. CLASSIFY – CKD

104. CKD:
CONT.…
GFR >90 ml/min: HPT +/- is frequent
GFR 60 – 89 ml/min: HPT frequent, PTH levels
start to rise.
GFR 30 – 59 ml/min: HPT, PTH markedly increased,
decreased calcium absorption, reduced phosphate
excretion, onset of anaemia, left ventricular
hypertrophy.
GFR 15 – 29 ml/min: triglyceride start to rise,
hyperphosphatemia, metabolic acidosis with
tendency to hyperkalaemia.

105. CKD:
TREATMENT
The first step in the treatment of chronic
kidney disease is to determine the underlying
cause
Some causes are reversible, including use of
medications that impair kidney function,
blockage in the urinary tract, or decreased
blood flow to the kidneys.
Treatment of reversible causes may prevent
CKD from worsening.

106. CKD: TREATMENT…
Hypertension
Hypertension in 80 to 85 % of people with CKD
Maintaining good BP control is the most important goal for trying to
slow the progression of CKD.
Angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor
blocker (ARB) reduces blood pressure and levels of protein in the urine,
and is thought to slow the progression of CKD to a greater extent than
some of the other medicines used to treat high blood pressure.
Sometimes, a diuretic or other medication is also added

107. CKD: TREATMENT…
Anaemia
People with CKD are at risk for anaemia
(This occurs because improperly functioning kidneys produce reduced
erythropoietin)
Selected patients can be treated with drugs that stimulate production of red
blood cells.
In some cases, iron supplements are also prescribed

108. CKD: TREATMENT…
Dietary changes:
 Changes in diet may be recommended to control or prevent some of the
complications of CKD; most important is salt restriction to help control the
blood pressure.
Potassium:
 Some people with CKD develop a high blood potassium level, which can
interfere with normal cell function. This is frequently treated with by shifting
potassium. Measures to prevent high potassium might also be recommended,
including a low potassium diet and avoiding medicines that raise potassium
levels

109. CKD: TREATMENT…
Protein:
 Restricting protein in the diet may slow the progression of CKD, although it is
not clear if the benefits of protein restriction are worth the difficulty of
sticking to a low protein diet.
Phosphate:
 Phosphate is a mineral that helps to keep the bones healthy. Early in the
course of CKD, the body begins to retain phosphate. As the disease
progresses, high blood phosphate levels can develop. This is usually treated
with medicines that prevent phosphate (found in foods) from being absorbed
in the digestive tract. Dietary phosphate restrictions are also recommended

110. CKD: TREATMENT…
Cholesterol and triglycerides
High cholesterol and triglyceride levels are common in people with CKD
High triglycerides have been associated with an increased risk of coronary artery
disease, which can lead to heart attack
Treatments to reduce the risk of coronary artery disease are usually
recommended, including dietary changes, medications for high triglyceride and
cholesterol levels, stopping smoking, and tight blood sugar control in people
with diabetes.

111. HIV AND CHRONIC
KIDNEY DISEASE

112. HIV & CKD
Renal disease is a relatively common complication in patients with human
immunodeficiency virus (HIV) disease.
It is a leading cause of end stage kidney disease among the HIV-1 seropositive
population.
HIV nephropathy can result from direct kidney infection with HIV or from the
adverse effects of antiretroviral drugs
It manifests as AIDS-defining late-stage illness (CD4 <200) or during the acute HIV
infection
Patients with HIV disease are at risk for developing prerenal azotaemia due to
volume depletion resulting from salt wasting, poor nutrition, nausea, or
vomiting.

113. EPIDEMIOLOGY
Prevalence of CKD in HIV-infected individuals varies broadly
 Africa: 38% Nigeria, 20% Uganda, 11.5% Kenya
 Asia: 16.8% Hong Kong, 27% India
 Americas: 7%
 Europe: 1%
HIV as etiologic factor of CKD
 Spain: 0.5-1.1%
 Cameroon: 6.6%
 South Africa: 28.5%
Source: https://kdigo.org/wp-content/uploads/2019/10/KDIGO-HIVAN-Presentation-Hägele-Coruna.pdf

114. Kaboré et al. BMC Nephrology (2019) 20:155https://doi.org/10.1186/s12882-019-1335-9

115. HIV
&
CKD
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4536633/pdf/clinnephrol-83-S032.pdf

116. HIV-
ASSOCIATED
NEPHROPATHY
(HIVAN)
First described in early 1980s associated with AIDS
Aggressive form of FSGS in African-Americans
Appears in a progressing HIV infection
Major cause of ESRD in HIV patients
Characterized by significant proteinuria and progressive
kidney failure.
Prevalence
•1% to 10% in HIV-infected patients
•HIVAN histology in 50% of HIV positive patients
•90% of HIVAN patients are of African descent.

117. HIVAN
Risk Factors
• Genetic predispositions: 18- to 50-
fold higher prevalence of HIVAN in
black HIV patients
• ART-related kidney toxicity
Tenofovir: 33% higher risk of CKD
Atazanavir: 20% higher CKD incidence
• Direct viral effects
• Comorbidity disease
Pathophysiology
• FSGS – a collapsing glomerulopathy
• Tubulointerstitial Nephritis
Key features/parameters of HIVAN:
• Advanced HIV disease
• Heavy proteinuria
• Rapid decline in kidney function

118. APPROACH TO TREATMENT
•Consider renal friendly regimen – ABC/3TC
•Avoid potentially nephrotoxic ARVs like TDF (glomerular & tubular toxicity)
•Renally adjust dose
HAART
•Maintain BP <130/80mmHg
•Antiproteinuric and reno-protective effect (these are independent of
antihypertensive effect)
•But may worsen hyperkalaemia
ACE-Inhibitors / ARBs

119. APPROACH
TO
TREATMENT
Adjustment of ART
Monitor E/U/Cr and Urine protein/creatinine ratio
Patients who progress to end-stage renal disease
(ESRD) require dialysis and consideration of renal
transplantation in carefully selected cases.

120. RENAL STONES
(NEPHROLITHIASIS)

121. RENAL
STONES
(NEPHROLITHIASIS)
Nephrolithiasis refers to calculi in the
kidneys.
Nephroliths are crystal aggregates of
dissolved minerals that form in the
kidneys as a result of abnormalities in
renal physiology and urine content

122. RENAL
STONES:
CAUSES
A high concentration of a substance in
the urine due to:
• low urine volume.
• high excretion rate
pH changes:
• alkaline urine predisposes to Ca deposition
(e.g., infection)
• acidic urine predisposes to uric acid
deposition
Stagnation, usually due to urinary tract
obstruction.

123. TYPES OF STONES (OR CALCULI)
The following are the 4 main chemical types of renal calculi:
• Calcium stones;
• Uric acid stones;
• Magnesium ammonium phosphate stones (struvite),
• and other rarer forms
Calcium Stones:
• Most kidney stones are calcium compounds.
• May be associated with conditions such as hyperparathyroidism.
• Examples:
• Ca-oxalate (+ phosphate)
• ca-phosphate

124. TYPES OF STONES
Uric Acid Stones
•Uric acid stones are formed in about 10% of gouty cases.
•May be associated with low urinary pH due to inadequate buffer production.
Magnesium Ammonium Phosphate Stones (Struvite)
•These are often large stones and often associated with infections (e.g., UTI).
•Occur more commonly in women
Rare Forms
•cystine: e.g., in cystinuria – arising from transport defect of dibasic amino acids and
cystine.
•xanthine: e.g., in xanthine oxidase deficiency

125. HISTORICAL FEATURES
Important information in the history include the following:
•Duration, characteristics, and location of pain
•History of urinary calculi
•Prior complications related to stone manipulation
•Urinary tract infections
•Loss of renal function
•Family history of calculi
•Solitary or transplanted kidney
•Chemical composition of previously passed stones

126. SYMPTOMS AND SIGNS
The hallmark of stones that obstruct the ureter or renal pelvis is excruciating,
intermittent pain that radiates from the flank to the groin or to the genital area
and inner thigh.
This particular type of pain, known as renal colic, is often described as one of the
strongest pain sensations known.
Renal colic caused by kidney stones is commonly accompanied by urinary
urgency, restlessness, haematuria, sweating, nausea, and vomiting.

127. TREATMENT
OPTIONS
These depend on the cause and presentation.
Options include:
 Acidification of urine
 Pain medications
 Antispasmodic medications
 Ureteroscopy
 Alpha blocker e.g. Terazosin and Tamsulosin relax
the musculature and facilitate passage of the stone
 Good hydration is a good preventive method. Drink
water throughout the day.

129. SOME
REFERENCES
 Clinical Medicine, Kumar and Clark
 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4536633/pdf/
clinnephrol-83-S032.pdf
 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6188440/
 https://kdigo.org/wp-content/uploads/2019/10/KDIGO-HIVAN-
Presentation-Hägele-Coruna.pdf
 https://www.ncbi.nlm.nih.gov/books/NBK333408/pdf/Booksh
elf_NBK333408.pdf
 https://bmcnephrol.biomedcentral.com/articles/10.1186/s1288
2-019-1335-9
 https://pubmed.ncbi.nlm.nih.gov/27422620/
 https://pubmed.ncbi.nlm.nih.gov/28717938/
 WSU White Book in Paediatrics 2016