Acute kidney injury/ acute renal failureDefinitionSignificant deterioration Of kidney functionOccur over hours or daysManifested as abrupt increased of cr and ureaImportant featuresOliguria (<400ml/24h)ComplicationsVolume overloadK+ incrMetabolic acidosisProblem arisedIsolated problemORMore commonly: severe illness, sepsis, trauma, surgery, nephrotic drugsEpidemiologyDm, hpt, elderly

Causes1.pre-renal (impaired perfusion HYPOPERFUSION of kidney w blood>autoreg to maintain gfr>fail to autoreg){hypovolemia, hypotension}-sepsis (systemic vasoD)-cirrhosis-congestive cardiac failure-renal artery stenosis-limited renal blood flow (impaired cardiac pump efficiency & vascular ds)-ace & nsaids (impaire autoreg)2. IntrinsicAcute tubular necrosis-damage of renal tubular cells dt -ischaemia (2’ to hypoperfusion) -vascular problem: vasculitis, cholesterol emboli, hemolytic-uremic synd, thrombotic thrombocytopenic purpura, GN, interstitial nrphritis, malignant incr bp-nephrotoxins (drugs like aminoglycosides; amphotericin B; tetracycline, radio contrast agent, uric acid crystals, hemoglobinuria, myeloma)3.post-renalUTI*hemolytic uremic syndrome: primarily a disease of infancy and early childhood and is classically characterized by the triad of microangiopathic hemolytic anemia, thrombocytopenia, and acute renal failure.

Presentation• The presentation will depend on the underlying cause and severity of AKI. There may be no symptoms

or signs, but oliguria (urine volume less than 0.5 ml/kg/hour) is common. There is an accumulation of fluid and nitrogenous waste products demonstrated by a rise in blood urea and creatinine.

Symptoms• Urine output:

– AKI is usually accompanied by oliguria or anuria. However polyuria may occur due to either reduced fluid reabsorption by damaged renal tubules, or the osmotic effect of accumulated metabolites.

– Abrupt anuria suggests an acute obstruction, acute and severe glomerulonephritis, or acute renal artery occlusion.

– Gradual diminution of urine output may indicate a urethral stricture or bladder outlet obstruction - eg, benign prostatic hyperplasia.

• Nausea, vomiting.• Dehydration.• Confusion.Signs• Hypertension.• Abdomen: may reveal a large, painless bladder typical of chronic urinary retention.• Dehydration with postural hypotension and no oedema.• Fluid overload with raised jugular venous pressure (JVP), pulmonary oedema and peripheral oedema.• Pallor, rash, bruising: petechiae, purpura, and nosebleeds may suggest inflammatory or vascular

disease, emboli or disseminated intravascular coagulation.• Pericardial rub.

1. When to suspect chronic renal failure?A: -comorbidity (dm, hpt)-long duration of sx-abN blood tests-USS –small kidney (<9cm) w incr echogenicity(absence of anemia/HYPOca2+/HYPERpo4-acute renal failure but this may not b true)

2. Why urinary tract obstruction imp to b identifiedA: -Uri tract obstr is reversible-prevent permanent renal damage

Chronic renal failureDefinitionKidney damage for =/> 3 months based on findings of abN structure or functionORGfr <60ml/min/1.73m2 for >3 months w or w/o evidence of kidney damage

Classification (stage)1(>90) N or high gfr (w evidence of renal damage)2(60-) slight low gfr (w)3a(45-) moderate low gfr (w or w/o)3b(30-)4(15-) severe low gfr (w or w/o)5(<15) established renal failure

*end stage renal failure-gfr<15ml/min/1.73m2

-need for renal replacement therapy (dialysis/transplant)

CausesCommon-dm-hptOthers-glomerulonephritis, interstitial nephritis, pyelonephritis-renovascular ds, polycystic ds, analgesic nephropathy-renal stone, bphRareSle, scleroderma, vasculitis, myeloma, amyloidosis

Signs and symptomsSigns of metabolic acidosis in stage 5 CKD include the following:• Protein-energy malnutrition (group of related disorders that

include marasmus, kwashiorkor, and intermediate states of marasmus-kwashiorkor.)

• Loss of lean body mass• Muscle weakness

Signs of alterations in the way the kidneys are handling salt and water in stage 5 include the following:• Peripheral edema• Pulmonary edema• Hypertension(fluid overload cause SOB and ankle swelling)

Anemia in CKD is associated with the following:• Fatigue, Reduced exercise capacity, Reduced quality of life• Impaired cognitive and immune function• Development of cardiovascular disease, New onset of heart failure or the

development of more severe heart failure, Increased cardiovascular mortality

Other manifestations of uremia in end-stage renal disease (ESRD), many of which are more likely in patients who are being inadequately dialyzed, include the following:(sx common when urea >40mmol/L, N urea is 2.5-7.5 )• Encephalopathy: Can progress to coma and death• Pericarditis: Can be complicated by cardiac tamponade, possibly resulting in

death• Gastrointestinal symptoms: Anorexia, nausea, vomiting, diarrhea• Peripheral neuropathy, Restless leg syndrome• Skin manifestations: Dry skin, pruritus, ecchymosis, Platelet dysfunction with

tendency to bleed• Fatigue, increased somnolence, failure to thrive, Malnutrition• Erectile dysfunction, decreased libido, amenorrhea

PE1. Inspect-pallor(anaemia)-skin: yellow skin pigmentation, purpura, bruising, ecchymoses (uremia), bleeding(plt)-nails:brown-proximal myopathy (dm-peripheral neuropathy)-incr bp (hpt?)2. Chest-apex beat deviate(cardiomegaly)- Pericardial rub(pericarditis 2’ to uremia)- Pleural effusion, Pulmonary edema3. Leg-Peripheral edema-hypotonia, weakness, arreflexia, sensory loss in stocking distribution (peripheral neuropathy dt dm)

Nephrotic syndrome• Pathophysiology

– Damage to the structure of glomerular basement membrane

Increased size or number of pore

Passage of more and large molecule

proteinuria

- Reduction of negatively charged component

Negatively charged protein molecules is not repel

proteinuria

• Pathophysiology– Protein loss in urine> hypoalbuminaemia– Red in oncotic pressure or retention of Na+>

oedema– Liver prudce more lipoproteins > hyperlipidaemia

• Criterias – Proteinuria >3-3.5g/24h– Hypoalbuminaemia <3g/dL– Peripheral oedema– Hyperlipidaemia

• Signs– Swelling : periorbital, facial, upper limb, lower limb,

abdomen (ascites)– Ascites : shifting dullness and fluid thrill– BP- high– Urine dipstick – hematuria– DVT

• Symptoms– Peripheral oedema : SOPD– Frothy urine

Minimal change disease

• Common in children (76%), adult (20%) male

• Ix – light microscopy normal, electron microscopy shows fusion of podocytes

• Association – hodgkin lymphoma, drugs(NSAIDS)

• Remit with steroids but prone to relapse. If frequent relapse or steroid dependence, cyclosporin or cyclophosphamide

• Prognosis – 1% ESRF• Pathogenesis

– It is postulated that MCD is a disorder of T cells, which release a cytokine that injures the glomerular epithelial foot processes (podocytes). This, in turn, leads to a decreased synthesis of polyanions. The polyanions constitute the normal charge barrier to the filtration of macromolecules, such as albumin. When the polyanions are damaged, leakage of albumin follows.

Focal segmental glomerulosclerosis

• Ix – light microscopy shows scarring of certain segment (focal sclerosis), immunofluroescence showsIgM and c3 deposit in affected areas

• Etiology – primary (idiopathic), secondary (IgA nephropathy, vesicoureteric reflux, Heroin, vasculitis, sicke cell)

• Mx – corticosteroids, cyclophosphamide or cyclosporin if steroid-resistance

• Prognosis – 50% ESRF• Pathogenesis

• viral- or toxin-mediated damage or intrarenal hemodynamic changes such as glomerular hyperperfusion and high intraglomerular capillary pressure. injury inherent within or directed to podocytes. Foot process effacement, proliferation of mesangial, endothelial, and epithelial cells in the early stages, followed by shrinkage/collapse of glomerular capillaries all lead to scarring (glomerulosclerosis).

Membranous nephropathy• Epidemiology

– 20-30% of nephrotic in adult• Association

– Malignancy– Infection– Autoimmune– Drugs

• Prognosis– Risk of renal vain thrombosis– 40%(oxford) half(kumar) spontaneous remission – 40% (kumar) CKD

• Diagnostic test– Renal biopsy: Light microscopy-thickened glomerular basement membrane– Immunofluorescent : IgG and c3

• Tx– Steroids + cyclophosphamide, chlorambucil if deteriorate

• MCD – electron microscope shows fusion of podocytes foot process

• Focal segmental glomerulosclerosis – light microscope shows scarring of the glomerulus; electron microscope shows fusion of podocyte foot process

• Membranous nephropathy – thickening of glomerular basement membrane

Membranous nephropathyCause• 80% idiopathic• Secondary

– Malignancy – lymphoma, ca

– Infection – hep b hep c, malaria, syphilis, leprosy

– Autoimmune – SLE– Toxin - gold

MCDCause• Primary• Secondary – Malignacy –

lymphoma, ca– Infection – HIV– Drugs – NSAIDs– Toxin – mercury/

lead

Focal seg glomerusclerosisCause• Idiopathic • Secondary– Vesicoureteric

reflux– Single kidney,

aging kidney– Infection – HIV– Drug - heroin

Diabetic nephropathy

• Clinical diagnosis– Macroalbuminuria– Hx of DM >10y– Microvascular complication : DM retinopathy

• Pathology – accumulation of extracellular matrix cause expansion of mesangial cell and interstitial expansion

• Ix – renal biopsy shows nodule and hyaline deposits in glomerular arterioles. Nodule= kimmelstiel-wilson lesion

*macroalbuminuria – presence of large amount of protein in the urine, often precede end stage renal disease

Complication

1. Infection – spontaneous bacterial peritonitis2. Hyperlipidaemia – due to incr lipoprotein

production and reduced catabolism, results in incr in the lipid profile

3. Hypercoagulability – DVT & renal vein thrombosis

4. Malnutrition