KIDNEYS

DR RICHARD K NYAMEKYE, @ L300, 2021,

PUCG
 Scope
• Basic structure and functions
• Drugs acting on kidneys –diuretics
• Acute kidney injury
• Chronic kidney disease
 BASIC STRUCTURE
• The kidneys are paired retroperitoneal organs
• Size in adults 11–14 cm in length, 5–6 cm in width and 3–4 cm
in depth.
• comprises an outer cortex and an inner medulla.
• The functional unit of the kidney is the nephron,
• approx. one million nephrons in each kidney
• Each nephron is made up of a glomerulus, proximal tubule, loop
of Henle, distal tubule and collecting duct.
nephron
Ultrafiltration of plasma
 Functions
• Excretion - Urea, Creatinine, Uric acid, Drugs, etc
• Water and Electrolyte balance - Sodium,
Potassium, Phosphate, etc
• Acid-base balance – bicarbonate production,
excretion of acids
• Blood Pressure regulation - RAAS
• Hormones – Erythropoetin, Vit D activation by 1 –
alpha hydroxylase
 Diuretics

• treatment of conditions of salt and water

retention and in hypertension
• They act by inhibiting sodium reabsorption
at various locations along the nephron
 proximal tubule

• carbonic anhydrase inhibitors such as

acetazolamide
• only a small fraction of sodium loss
• not very useful clinically, except in treating
hydrocephalus (reduces CSF production)
 loop of Henle

• Loop diuretics such as furosemide (Lasix)

• blocks Na,K,2Cl co-transporter.
• Potent diuretics
• commonly used to reduce significant oedema.
• Adverse effect – hyponatremia, hypokalemia,
 early distal tubule
• Thiazides such as bendrofluthiazide,
hydrochlorothiazide
• block the sodium–chloride cotransporter
• less potent than loop diuretics
• Widely used in the treatment of hypertension and less
severe oedema
• Adverse effect – hypokalemia, hyperglycemia,
hyperuricemia,
late distal tubule/collecting duct

• potassium-sparing diuretics – does not block

excretion of potassium. May cause hyperkalaemia.
• blocks apical sodium channel, e.g amiloride
• Most widely used – spironolactone, is a
mineralocorticoid receptor blocker
 Osmotic diuretics

• act independently of specific transport

mechanisms
• They retain fluid osmotically within the
tubular lumen
• E.g Mannitol - given by intravenous
infusion to reduce cerebral oedema.
 Acute kidney injury - AKI

• Defined as a rapid decline in GFR and retention

of nitrogenous waste as products over a span of
days to weeks.
• Often accompanied by reduction in urine volume,
salt and water retention
 3 categories of AKI

• Prerenal
• Intrinsic renal
• postrenal
 Prerenal AKI

• volume depletion - bleeding, diarrhea and

vomiting, Third space loss (intestinal obstruction,
liver cirrhosis)
• Decreased cardiac output - Congestive heart
failure
• Sepsis,
• ACEi in bilateral Renal artery stenosis,
• NSAIDS in volume depleted patients
 Intrinsic AKI
• Glomerulonephritis
• malignant hypertension
• pre-eclampsia,
• Contrast induced nephropathy
• Nephrotoxic drugs, e.g aminoglycosides,
certain herbs
• HUS-TTP, DIC
• Acute Tubular Necrosis (ATN) – from
ischemia
• Intratubular Obstruction e.g hemolysis in
SCD, G6PD
 Postrenal AKI

• Prostate disease – BPH, Prostate cancer

• Stone
• schistosomiasis
• Urethral disease - posterior urethral valve
• Bladder tumours
 Treatment - AKI
Treatment is largely supportive
Maintain renal perfusion – adequate hydration
Treat underlying cause, e.g sepsis, gastroenteritis
Stop any offending drug
Relieve obstruction if postrenal – e.g pass urethral
catheter
Monitor fluid input and urine output
May require dialysis if severe
 Chronic kidney disease (CKD)
• is an irreversible deterioration in renal
function which usually develops over a period
of years
• Renal function is estimated by calculating GFR
• GFR Equations in adults commonly are:
• 1. Cockcroft-Gault equation
• 2. MDRD
• 3. CKD-EPI
 Aetiology
• 20-30% unknown
• Systemic disease
• Diabetes Mellitus
• Hypertension
• HIVAN
• Chronic Glomerulonephritis
• Chronic Pyelonephritis
• Chronic schistosomiasis
• drug-induced, esp herbal
• Systemic lupus erythematosus
• Sickle cell nephropathy
• ADPKD – autosomal dominant
polycystic kidney disease
 symptoms
• Early morning facial puffiness • Paraesthesiae due to
• Oliguria polyneuropathy

• Bipedal edema or anasarca • ‘Restless legs’ syndrome

• Malaise, loss of energy • Bone pain due to metabolic
bone disease
• Loss of appetite
• tetany due to hypocalcaemia
• Insomnia
• pulmonary oedema
• Nocturia and polyuria due to
impaired concentrating ability • Symptoms due to anaemia

• Itching • Amenorrhoea in women;

erectile dysfunction in men
• Nausea, vomiting and diarrhoea
 Uremic encephalopathy
• In more advanced CKD (stage 5), there are more
severe CNS symptoms:
• Mental slowing
• clouding of consciousness
• seizures
• Myoclonic twitching
• Also Uremic pericarditis and Uremic ‘frost’(i.e.
deposition of urea and urate on skin )
 Investigations
• To confirm diagnosis, identify the underlying
cause and determine any complications
• Urinalysis – proteinuria, hematuria, casts
• Blood Urea and creatinine – calculate the eGFR
for staging.
• Electrolytes – hyperkalemia common, also hyper
or hyponatremia
• Serum calcium and phosphates – typically
hypocalcemia and hyperphosphatemia
• FBC – anaemia
• Tests to R/o sickle cell disease
• HIV, hepatitis B and C screening
• Antistreptolysin O titre (ASOT), anti-DNAse
B) if PSGN likely
• ANA if SLE likely
• FBS /HbA1c for DM monitoring
• Abdominal Ultrasound – necessary for every patient
• CKD on ultrasound usually small kidneys with poor
corticomedullary differentiation
• CKD with normal renal size – DM nephropathy,
HIVAN, amyloidosis
• USG also r/o hydronephrosis), stones or ADPKD
• Renal biopsy - unexplained CKD and normal-sized
kidneys, unless there are strong contraindications.
• Complications of chronic kidney
disease
 Anemia
• Erythropoietin deficiency (the most significant)
• Bone marrow suppression from uraemia
• Bone marrow fibrosis secondary to
hyperparathyroidism
• Haematinic deficiency (anorexia and vomiting)– iron,
vitamin B12, folate
• Reduced red-cell survival .
• Increased blood loss – occult gastrointestinal bleeding,
blood loss during haemodialysis, platelet dysfunction
 Renal osteodystrophy
• 1. Osteomalacia
• 2. Osteoporosis
• 3. hyperparathyroid bone disease
• These occur due to decreased renal
production of the 1α-hydroxylase enzyme
resulting in low levels of active vitamin D.
• Causes low calcium levels and increased
PTH levels (secondary hyperparathyroidism)
 Skin disease

• Pruritus - due to uraemia, hypercalcaemia,

hyperphosphataemia,
• no effective treatment exists for the pruritus
• dry skin
• Eczematous lesions
 Gastrointestinal complications

• Uraemic gastritis
• reflux oesophagitis
• acute pancreatitis
• constipation
 Metabolic abnormalities
• Gout – Uric acid retention. Treated
with allopurinol
• hypoglycemia – reduced insulin
requirements in diabetics
• Lipid metabolism –
Hypercholesterolaemia. Treated with
statins (HMG-CoA reductase inhibitor)
e.g atorvastatin
 Endocrine abnormalities

• Hyperprolactinaemia - present with

galactorrhoea
• Decreased serum testosterone levels - Erectile
dysfunction and decreased spermatogenesis are
common
• Absence of normal cyclical changes in female
sex hormones, resulting in oligomenorrhoea or
amenorrhoea
Central nervous system = uraemic encephalopathy

• depressed cerebral function and decreased

seizure threshold.
• Asterixis, tremor and myoclonus
• Dementia
• Psychiatric - anxiety, depression, and
psychoses
 Other complications

• Uraemic pericarditis
• Hypertension
• Pulmonary edema, and fluid overload
• Hyperkalemia
Risk factors for Progression of CKD

• Proteinuria
• Hypertension
• Diabetes
• Smoking
• Hyperlipidemia
• Nephrotoxic drugs
 Treatment
Goals of treatment:
• Minimize the risk of any additional renal
injury.
• Avoid nephrotoxic drugs.
• Reduce the risk of death from
Cardiovascular disease
• Reduce the rate of progression.
• Manage the complications
 Reducing the rate progression
• Treat the primary disease – e.g Treat diabetes
(HbA1c <7%,)
• Keep BP< 120/80mmHg
• ACE inhibitor/ angiotensin receptor antagonist
- reduce proteinuria
• Loop diuretic – increase urine output, prevent
hyperkalaemia and help BP control
• Statins to lower cholesterol to <4.5 mmol/L
• Stop smoking (three-fold higher rate of
deterioration in CKD)
• Normal protein diet
 Manage complications
• Anaemia – give s.c erythropoietin, hematinics,
transfuse if severe
• Pulmonary edema, oliguria – give furosemide
• Hyperkalemia- calcium gluconate, salbutamol
nebulization, insulin + 50%dextrose, frusemide,
kayexalate, dialysis if refractory
• Hypertension – ACEi/ARBs, CCBs, etc
• Hypocalcemia/hyperphosphatemia – give calcium
carbonate and vit D
• Erectile dysfunction - The oral phosphodiesterase
 Renal replacement therapy
• to mimic the excretory functions of the normal
kidney
• excretion of nitrogenous wastes
• maintenance of normal electrolyte
concentrations
• maintenance of a normal extracellular volume.
• E.g hemodialysis, peritoneal dialysis
• Best long term treatment - kidney transplant
 references
• Firth John D, Medical Masterclass, Endocrinology, Ed 2nd,
2010
• Davidson’s Principles and Practice of Medicine, Ed 22nd,
2014
• Kumar and Clark’s Clinical Medicine, Ed 8th, 2012