UKMLA: Nephrology

AIN: What is it?

Intrinsic cause of AKI due to a triad of:

• Fever

• Macular/maculopapular rash

• Eosinophilia

AIN: What is the most common cause?

Drugs:

• Antibiotics

• NSAIDS

• PPI’s

• Warfarin

• Phenytoin

AIN: Which autoimmmune conditions are associated with it?

• SLE

• Sarcoidosis

• Sjogren syndrome

• TIN with uveitis

AIN: What is tested during the autoimmune screen to identify if the cause is autoimmune?

• ANA (antinuclear antibody)

• ANCA (anti-neutrophil cytoplasmic antibody)

• Anti-double stranded DNA

• Complement

AIN: What is the management?

• Steroids if AIN is due to autoimmune condition

• Oral prednisolone if AIN is due to drugs

• Diuretics for fluid overload

AKI: What is AKI?

A reversible kidney injury that occurs within hours and is characterised by either:

• Hypovolaemia

• Uvolaemia

• Hypervolaemia

AKI: What are the risk factors?

Patients at increased risk of AKI include:

• Patients with CKD

• Elderly patients

• Previous AKI

• Malignancy

• Medical conditions increasing risk of urinary obstruction (e.g. benign prostatic hyperplasia)

• Cognitive impairment and disability (may be reliant on others for fluid intake)

• Recent use of medications such as NSAIDs or ACE inhibitors

• Recent administration of iodine-containing contrast media

AKI: What are the PRE-RENAL causes?

Decreased renal perfusion due to:

• Hypovolaemia (burns, dehydration etc)

• NSAIDS, ACEi, ARBS, diuretics

• Heart failure

• Sepsis

AKI: What are the RENAL causes?

Structural damage to the kidneys due to:

• Glomerulonephritis

• Nephrotic syndrome

• Acute tubular necrosis

• Rhabdomyolysis

• Renal vein thrombosis

AKI: What are the POST-RENAL causes?

• Luminal→ stones or blocked catheter

• BPH

AKI: What is stage 1 AKI?

Any of the following:

• Creatinine rise of 26 micromol/L or more within 48 hours

• Creatinine rise to 1.5-1.99x baseline within 7 days

• Urine output < 0.5 mL/kg/hour for more than 6 hours

AKI: What is stage 2 AKI?

Any of the following:

• Creatinine rise to 2-2.99x baseline within 7 days

• Urine output < than 0.5 mL/kg/hour for more than 12 hours

AKI: What is stage 3 AKI?

Any of the following:

• Creatinine rise to 3x baseline or higher within 7 days

• Creatinine rise to 354 micromol/L or more with either:

  • Acute rise of 26 micromol/L or more within 48 hours or

  • 50% or more rise within 7 days

• Urine output < than 0.3 mL/kg/hour for 24 hours

• Anuria for 12 hours

AKI: What are the symptoms?

• Can be asymptomatic and detected via bloods

• Nausea and vomiting

• Low urine output

• Dark urine

• Fatigue

• Confusion

• Anorexia

• Pruritus

AKI: What are the signs?

On examination, look for:

• Hypertension (a complication of AKI)

• Bladder distension due to urinary retention

• Hypotension and dehydration (in many pre-renal causes)

• Signs of fluid overload (e.g. raised jugular venous pressure, pulmonary and peripheral oedema) as a complication of AKI

• Signs related to the underlying cause (e.g., fevers in sepsis, rashes in vasculitis)

• Pericardial rub (in uraemic pericarditis)

AKI: What are the blood test investigations?

• Urinalysis→ raised WBC

• ECG→ hyperkalaemia (if acute, QRS will be wide, flat p waves and tall tented T waves→ dialysis!)

• ABG→ acidosis

• U&E→ creatinine levels

• Creatinine kinase→ rhabdomyolysis

AKI: What are the imaging investigations?

• Bladder scans

• US of kidney, ureters and bladder (US-KUB)

• CT of kidney, ureters and bladder (CT-KUB)

AKI: What is the management?

IV fluid resuscitation

Catheter

Correct any electrolyte imbalances

Stop any nephrotoxic drugs

AKI: What is the ‘AEIOU’ criteria for referral to renal replacement therapy?

• Acidosis

• Electrolyte imbalance (hyperkalaemia)

• Intoxication (drugs or poison)

• Oedema

• Uraemia (encephalopathy or pericarditis)

AKI: What are the components of a renal screen?

Protein electrophoresis

C3

C5

ANA

DsDNA

ANCA

Anti-GBM

Immunoglobulins

Erythrocyte sedimentation rate

HIV screening

Hepatitis B and C serology

AKI: What are the causes of tubular-interstitial nephritis?

• PPI’s

• Penicillin and macrolide antibiotics

• Sarcoidosis

• Rhabdomyolysis

AKI: Which drugs are nephrotoxic?

• Tacrolimus

• NSAIDS

• Gentamycin

• Imaging contrast

AKI: What are the causes of glomerularnephritis?

• SLE

• Good Pasteur’s disease

• Post-strep infection

• Haemolytic uraemic syndrome

AKI: What is the difference between nephrotic and nephritic syndrome?

• Nephrotic→ heavy proteinuria

• Nephritic→ heavy haematuria, loss of proteins

AKI: Which drugs improves CKD but worsens AKI due to hyperkalaemia?

ACEi

ATN: What is it?

• Most common intrinsic (renal) cause of AKI

• Due to renal tubular epithelial cell damage

• This may be due to nephrotoxic drugs or ischaemia

ATN: What are the risk factors?

• Hypovolaemia

• Old age

• CKD

• Nephrotoxic drugs

ATN: What are some examples of nephrotoxic medications?

• Aminoglycoside antibiotics (e.g. gentamicin)

• Antifungals (e.g. amphotericin)

• Chemotherapy agents (e.g. cisplatin)

• Antivirals (e.g. tenofovir)

• Nonsteroidal anti-inflammatory drugs (NSAIDs)

• Contrast agents

• Myoglobin (rhabdomyolysis)

ATN: What are the symptoms?

• Lethargy and malaise

• Nausea and vomiting

• Oliguria or anuria (polyuria may be seen in the recovery phase)

• Confusion

• Drowsiness

• Peripheral oedema

ATN: What are the bedside investigations?

• Urine microscopy→ muddy brown granular cases

• Urinary sodium is high (>40)

• Urine osmolality is low (<450)

• VBG for acidosis and hyperkalaemia

ATN: What are the bloods investigations?

• U&Es

• Urea:creatinine ratio is low

• FBC

• Creatine kinase to rule out rhabdomyolysis

• LFT CRP

• Blood cultures

• Coagulation screen

ATN: What is the management?

• Stop nephrotoxic drugs

• Catheter if needed

• Treat underlying cause

• IV fluids for hypovolaemia ± hypotension

• Blood products if due to haemorrhage

• If severe, dialysis may be indicated

Anti-GBM Disease: What is it?

Previously called “good pasteur’s disease”→ a life-threatening autoimmune condition characterised by:

• Anti-GBM antibodies

• Rapidly progressive glomerulonephritis

• Pulmonary necrotising haemorrhage

Anti-GBM Disease: What is the epidemiology?

Rare, most affects men, 20-30 y/o and 60-70 y/o

Anti-GBM Disease: What is the cause?

IgG antibodies fight against type 4 collagen resulting in a type 2 hypersensitivity reaction = inflammation

Anti-GBM Disease: What are the risk factors?

• HLA-DRB1 gene

• Smoking

• Exposure to solvents, metal dusts etc.

• Infections e.g. ifluenza

• Alemtuzumab (multiple sclerosis drug)

• Alport syndrome

Anti-GBM Disease: What are the symptoms?

• Haematuria

• Cough ± haemoptysis

• Chest pain

• Sob

• Lethargy

• Anorexia

• Myalgia

• Arthralgia

Anti-GBM Disease: What are the signs?

• HTN

• Oligouria or anuria

• Tachypnoea

• Crackles heard in the lower zones of lungs

• Cyanosis

• Pallor (due to anaemia)

• Fever

Anti-GBM Disease: What are the investigations?

• Anti-GBM antibodies

• Complement levels→ would be low in anti-GBM disease

• Urinalysis→ confirm haematuria and proteinuria

• Albumin:creatinine ratio

• VBG→ check for hyperkalaemia

• FBC→ haemarrhage can cause anaemia

Anti-GBM Disease: What is the gold standard investigation?

Renal biopsy

Anti-GBM Disease: What is the management?

1. Methylprednisolone (6 months) AND cyclophosphamide (2-3 months)

2. Once anti-GBM antibodies aren’t detectable anymore, perform plasmaphoresis

ADPKD: What is it?

Autosomal Dominant Polycystic Kidney Disease (ADPKD) is an inherited renal disorder characterised by continuous formation and growth of cysts in the kidneys.

This leads to progressive renal impairment due to destruction of nephrons and may cause end-stage kidney disease (ESKD).

ADPKD: What is the cause?

Autosomal dominant inheritance of:

• PKD1 polycystin gene on chromosome 16

• PKD2 polycystin gene on chromosome 4

ADPKD: What are the symptoms?

• Flank pain

• Chronic pain

• Haematuria

• Systemic illness (fever etc)

• Recurrent UTI

• Polyuria

• Nocturnal

• CKD

ADPKD: What are the expected examination findings?

• Bilateral large masses in the flanks (palpable enlarged kidneys)

• Hepatomegaly (up to 70% have liver cysts)

• Hypertension

• Splenomegaly is rarer (5% have splenic cysts)

ADPKD: What are the expected blood results?

• FBC→ polycythaemia due to excessive EPO

• LFT→ normal

ADPKD: What is the key diagnostic test?

US kidneys:

• 3+ renal cysts in total if aged 15-39 is sufficient to diagnose ADPKD

• 2+ cysts in each kidney if aged 40-59 is sufficient to diagnose ADPKD

• No cysts if aged 40+ is sufficient to exclude ADPKD

ADPKD: What is the management?

• Avoid nephrotoxic drugs and oestrogens (promote hepatic cyst growth)

• Tolvaptan is an option for patients with stage 2 or 3 CKD with rapidly progressive disease, to slow cyst growth and renal impairment

• Antihypertensives may be required to maintain a blood pressure of < 130/80→ ACE inhibitors or angiotensin-II receptor antagonists are first-line

• Surgical drainage of cysts

• Nephrectomy

CKD: What is CKD?

Abnormal kidney function or structure for over 3 months

CKD: What is the diagnostic criteria?

• GFR below 60 on at least 2 occasions, 90 days apart.

• Urinary albumin:creatinine ratio > 3 mg/mmol

• Acidosis or electrolyte imbalances

• Previous renal transplant

CKD: What is the most common cause?

Diabetes

CKD: What are the risk factors?

• FH of CKD

• Black or Hispanic ethnicity

• History of AKI

• Older age (>75 y/o)

CKD: Which evidence of kidney damage is considered in KDIGO CKD staging criteria?

• Biopsy-proven chronic glomerulonephritis

• Persistent haematuria

• Persistent microalbuminuria

• Persistent proteinuria

• Evidence of hereditary kidney disease

CKD: What is stage 1 CKD according to the KDIGO criteria?

eGFR over 90 and kidney damage (haematuria, proteinuria, or renal anatomical abnormality)

CKD: What is stage 2 CKD according to the KDIGO criteria?

eGFR of 60-89 and kidney damage (haematuria, proteinuria, or renal anatomical abnormality)

CKD: What is stage 3 CKD according to the KDIGO criteria?

3a) eGFR of 45-59

3b) eGFR 30-44

CKD: What is stage 4 CKD according to the KDIGO criteria?

eGFR Of 15-29

CKD: What is stage 5 CKD according to the KDIGO criteria?

eGFR less than 15

CKD: What are the symptoms?

• Lethargy

• Anorexia

• Headaches

• Uraemic pruitus

• SOB

• Muscle cramps especially at night

• Bone pain

• Taste changes

• Frothy urine

• Pallor

• Dehydration

CKD: What are the non-CKD causes of a low eGFR?

High serum creatine result due to high muscle mass or after consumption of meat

CKD: What are the non-CKD causes of a high albumin:creatinine ratio? (ACR)

Menstruation, UTI or strenuous exercise

CKD: What are the investigations?

• Urine dipstick → screen for haematuria/proteinuria

• Early morning albumin:creatinine ratio → repeat within 3 months if it is between 3-70 mg/mmol

• U&E’s → repeat within 2 weeks if eGFR is <60

• FBC

• LFT→ raised ALP

• Bone profile→ raised phosphate

• PTH

• HIV and hepatitis B/C serology

• HbA1c→ diabetes

CKD: What is the MEDICAL management?

1. Treat the underlying cause e.g. diabetes

2. Review medications→ stop nephrotoxic drugs

3. Treat HTN

4. Give atorvorstatin to reduce lipid levels

5. Give aspirin for secondary cardiovascular disease prevention

6. Annual influenza vaccination

7. 5-yearly pneumococcal vaccine

CKD: Which drug should be given to diabetic patients with CKD?

If the ACR value is >2.5mg/mmol in men or >3.5mg/mmol in women, diabetic patients should be started on an ACE inhibitor

CKD: What is the SURGICAL management?

Renal replacement therapy (haemodialysis, peritoneal dialysis, renal transplant etc)

CKD: What is the criteria for renal replacement therapy?

• eGFR approximately 5-7 ml/min/1.73m_

• Symptomatic uraemia affecting quality of life

• Refractory fluid overload

• Refractory biochemical abnormalities

CKD: What are the complications?

• Anaemia (normochromic or normocytic)

• Hyperparathyroidism

• Cardiovascular disease

• Uraemia

• Hyperkalaemia

• Metabolic acidosis

• Fluid overload

• Malnutrition

• Malignancy

• HTN

• Poor mental health

CKD: What are the target Hb levels in CKD patients?

>100 g/L. If Hb is lower and ferritin is normal, deliver regular subcutaneous erythropoietin injections

(The transferrin saturation should be >20% and ferritin >200ng/mL before EPO treatment. If it isn’t, give IV iron first)

CKD: How do you differentiate between AKI and CKD?

Renal US→ in CKD patients will have bi-lateral shrunken kidneys if they have end-stage renal disease

DKD: What is the most common cause of end-stage renal failure?

Diabetic kidney disease

DKD: What are the risk factors?

• HTN

• Obese

• Diabetic retinopathy

• Male

• Smoker

• South Asian

• Dyslipidaemia

DKD: What is class 1 diabetic kidney disease?

Histological findings:

Thick glomerular basement membrane

DKD: What is class 2 diabetic kidney disease?

Histological finding:

Diffuse mesangial expansion

DKD: What is class 3 diabetic kidney disease?

Histological finding:

Nodular sclerosis (kimmelsteil-Wilson lesions)

DKD: What is class 4 diabetic kidney disease?

Histological finding:

Advanced glomerulosclerosis affecting more than 50% of glomeruli

DKD: What are the symptoms of later stage diabetic kidney disease?

• Fatigue

• Anorexia

• Weight loss

• Taste disturbance

• Itch

• SOB

• Bone pain

• Foamy urine

• Polyuria

• Oligouria

• Nausea or vomiting

DKD: What are the signs of later stage diabetic kidney disease?

• HTN

• Oedema

• Encephalopathy

• Cachexia

• Pallor

• Uraemic odour

DKD: What is the management?

• Conservative

• Target HbA1c in these patients is 53 mmol/L

• If the ACR value is over 3 mg/mmol, give an ACEi (first-line)

• If the ACR value is 3-30 mg/mmol, give an SGLT2i

Dialysis: What are the two types?

• Haemodialysis → where a machine is used for filtration

• Peritoneal dialysis→ where the patient's peritoneum is used for filtration

Dialysis: What is an ‘arteriovenous fistula’ vascular access?

Arteriovenous fistula:

• An artery and vein are joined surgically, usually the radial artery and cephalic vein

• This increases the flow rate of blood as capillaries are bypassed

• An AV fistula needs to be created at least 4-8 weeks prior to use to give it time to mature

Dialysis: What is an ‘arteriovenous graft’ vascular access?

• A synthetic or natural graft is used to join an artery and vein

• This is more likely to clot or stenose than an AV fistula

Dialysis: What is a ‘tunnelled vascular catheter’ vascular access?

• Usually inserted into the internal jugular vein

• Wider bore access than a normal central line

• Tunnelling under the skin reduces infection risk

• May be used temporarily whilst an AV fistula matures or if a fistula or graft has failed

• Can also provide semipermanent access if a fistula or graft are not suitable

Dialysis: What is a ‘non-tunnelled vascular catheter’ vascular access?

• Temporary access only so often used in emergencies

• Internal jugular catheters may stay in for 2-3 weeks

• Femoral lines need removal within a week due to a higher risk of infection

Dialysis: How does peritoneal dialysis work?

• Peritoneal dialysis involves using the patient's own peritoneal membrane for filtration

• A peritoneal catheter is placed through which dialysate fluid is introduced into the abdominal cavity

• The fluid is then left for 1-4 hours in the abdomen whilst toxins and excess fluid diffuse into the dialysate fluid

• The fluid is then drained out via the peritoneal catheter and discarded

• Each cycle of this is called an "exchange"

Dialysis: What are the two types of peritoneal dialysis?

• Continuous Ambulatory Peritoneal Dialysis (CAPD) → 3-5 exchanges per day

• Automated Peritoneal Dialysis (APD) →involves a machine performing exchanges overnight

• Some people on APD also need to do a CAPD exchange once per day

Dialysis: What are the indications for dialysis?

• eGFR of 5-7 ml/min/1.73m2

• Symptoms of uraemia (e.g. malaise, nausea, pruritus)

• Fluid overload refractory to medical treatment

• Resistant hyperkalaemia

• Resistant acidosis

Dialysis: What are the complications of haemodialysis?

• Hypotension

• Muscle cramps

• Arrhythmias

• AV fistula may bleed

• Bacteraemia due to frequent vascular access → may lead to infective endocarditis

• Heparin-induced thrombocytopenia

Dialysis: What is the main complication of peritoneal dialysis?

Bacterial peritonitis:

• Symptoms include abdominal pain and cloudy dialysis effluent with >100 white cells per ml

• Managed via vancomycin and ceftazidime

Dialysis: What is the prognosis?

• Patients receiving dialysis have a significantly increased risk of death compared to the general population

• The highest risk of death is in the first 90 days after starting dialysis

Glomerulonephritis: What is it?

A disease of the glomerulus as classified based on the presenting clinical syndrome, histological appearance, causes etc

Glomerulonephritis: Which conditions are associated with it?

• Nephritic syndrome

• IgA nephropathy

• Post-strep glomerulonephritis (PSGN)

• Post-infection glomerulonephritis

• ANCA- associated vasculitis (AAV)

Glomerulonephritis: What is the most common cause?

IgA nephropathy→ due to IgA deposition in the mesangium of the glomerulus

(IGAN) Glomerulonephritis: What are the clinical features of IgA nephropathy?

• Haematuria 12-72 hours after URT infection or GI infection

• 20-30 y/o

• HTN

• Associated with vasculitis, chronic liver disease, IBD, skin and joint disorders e.g. psoriasis

(IGAN) Glomerulonephritis: What are the investigations of IgA nephropathy?

• Urinalysis is typically positive for blood ± protein; it is rare for patients to present with nephrotic-range proteinuria

• Urine microscopy will usually show presence of dysmorphic red blood cells which suggests bleeding from the glomerulus

• The gold-standard method for diagnosis is renal biopsy:

  • This shows diffuse mesiangial IgA immune complex deposition

• Serum IgA is elevated in approximately 50% of patients

(IGAN) Glomerulonephritis: What is the management of IgA nephropathy?

• Dietary salt restriction

• Treatment of proteinuria (>0.5 g/day) with an ACE-i/ARB

• Treatment of HTN

• High risk patients will be offered corticosteroids

(PSGN) Glomerulonephritis: What is post-streptococcal glomerulonephritis?

Occurs 1-3 weeks after strep throat→ common in children

(PSGN) Glomerulonephritis: What are the clinical features of post-streptococcal glomerulonephritis?

• Patients typically present with sudden onset of haematuria, oliguria, HTN and/or oedema 1-3 weeks post-infection

• Patients may also be asymptomatic with microscopic haematuria

(PSGN) Glomerulonephritis: What are the investigations of post-streptococcal glomerulonephritis?

• First-line investigation includes a urinalysis and MC&S:

  • Urinalysis is typically positive for blood ± protein

  • Urine microscopy will usually show presence of dysmorphic red blood cells which suggests bleeding from the glomerulus

• An FBC may show raised white cells, suggestive of an infective process

• U&Es often show an AKI

• The gold-standard method for diagnosis in adults is a renal biopsy: the classical finding is subepithelial 'humps' on electron microscopy

(MPGN) Glomerulonephritis: What is membranoproliferative glomerulonephritis?

It is thought to be caused by immune-complex deposition and complement activation and is associated with:

• hepatitis c

HUS: What is haemolytic uraemic syndrome?

A triad of:

1. Microangiopathic haemolytic anaemia

2. Thrombocytopaenia

3. AKI (raised creatinine)