Changes in urine volume

Nephrotic syndromeEtiology: Primary: Minimal change disease, membranous nephropathy, focal segmental glomerulosclerosis

Secondary: Diabetic nephropathy, SLE, amyloidosis, infections (eg: HBV, HCV, HIV), malignancy (lymphoma, leukemia)

Pathophysiology: Increase permeability of the filtration barrier, loss of negative charge of the membrane

Symptoms: Hypoalbuminaemia, Proteinuria (>3.5g/day), Oedema, Hyperlipidemia, Hypercoagulability, Immunosuppression

Nephritic syndromeEtiology: Primary: Post streptococcal glomerulonephritis, IgA nephropathy, Membranoproliferative glomerulonephritis, Rapidly progressive glomerulonephritis

Secondary: Goodpasture syndrome, SLE, Henoch-Schonlein purpura

Pathophysiology: Cellular proliferation in glomerulus (mesangial and endothelial), presence of inflammatory cells (neutrophils, macrophages)

Symptoms: Hematuria, Proteinuria, Hypertension, Oliguria, Uremia

Management of glomerular diseaseInvestigation:Urine FEME- detect RBC, WBC, cast, bacteria

24 hour urine collection- determine total urine proteinSerology- determine underlying causeRenal biopsy- determine pattern of glomerular damage

Treatment: If secondary, treat underlying causeIf primary, use immunosuppressive therapyACEI for antiproteinuric effect (caution in renal impairment)

Case Scenario

Mrs BE , 35 years old , presents with fever , arthralgia and rash for 4 days.She has been unwell for around 2 months. Her problems began with symptoms of dyspepsia , which started after taking some ibuprofen for her knee pain which she developed after a car accident in year 2010.

Initially she had self-medicated with Gaviscon and ranitidine (obtained from her local pharmacy), but her indigestion became so severe that around 1 month ago she attended her GP.

She was prescribed omeprazole which relieved her symptoms within a few days. About a week later she noticed a faint red rash on her arms. Since then, she has felt increasingly unwell with daily fevers, arthralgia of the small joints of the hand and intermittent loin pain.

There is no history of upper or lower respiratory tract symptoms. Her only other regularmedication is the OCP, which she has been taking for 7 years.She has no past medical history or family history of renal or autoimmune disease.She does not smoke nor does she drink alcohol. Works as an accountant.

PHYSICAL EXAMINATION

•Temperature : 37.4 degree Celsius

•Blood pressure : 145 / 90 mm Hg

•Erythematous , macular rash predominantly over the dorsum of the forearms as well as the legs

•Mild tenderness in both flanks

•Examination is otherwise unremarkable

INVESTIGATIONS

● Full blood count – Hb 12.1 g/dL WBC 11.1 × 10^9/L (eosinophils 1.2, normal range : 0.04–0.44), Platelets 534 × 10^ 9 /L

● Urine dipstick : Protein +++ , blood ++ , leucocytes +● ESR - 48 mm/h, CRP - 36 mg/L, ● LFT -normal, Albumin 34 g/L

Acute Kidney Injury

- Previously known as Acute renal failure

- Abrupt and often but not necessarily reversible loss of renal function, which develops over hours to days and is characterised by rise in serum creatinine and urea often together with oliguria or anuria

3 Categories of Acute Kidney Injury

1. Pre-renal AKI

2. Renal AKI

3. Post-renal AKI

1. Pre-renal AKI

Any cause of hypoperfusion: - hypoperfusion- hypovolemia- low oncotic pressure- congestive heart failure- constrictive pericarditis- renal artery stenosis

Diagnostic Testing for Pre-renal AKI

1. BUN to creatinine ratio of >15:1 and often >20:1

2. Urinary sodium is low (<20)3. Fractional excretion of sodium <1 percent (a

low urine sodium)4. Urine osmolality >5005. Hyaline casts

2. Renal AKI- Tubular injury: acute tubular necrosis, ATN

- Ischemia, contrast dye, myeloma, heme pigment (rhabdomyolysis)

- Interstitium: acute interstitial nephritis, AIN - Allergic and drug reactions - Infections (HIV and toxoplasmosis)

- Glomerular: glomerulonephritis

Diagnostic Testing for Renal AKI

1. BUN to creatinine ratio closer to 10:12. Urinary sodium >403. Urine osmolality <350

3. Post-renal AKI (obstructive uropathy)

Any cause of obstruction:- stone in the bladder or ureters- strictures- cancer of the bladder, prostate or cervix- neurogenic bladder (atonic or noncontractile,

such as from multiple sclerosis or diabetes)

Diagnostic Testing for Post-renal AKI

1. Urinalysis: frequently normal

2. Elevated BUN-to-creatinine ratio of >15:1

3. Haematuria if stones, hemorrhage, malignancy, or prostatic hypertrophy

Investigations

•Urine FEME

•Blood – BUN , creatinine , ABG , Calcium , phosphate

•X-rays (KUB)

•Ultrasound (KUB)

•Intravenous urography

•CT abdomen

•Renal biopsy

Management ● Administer glucose and insulin to correct hyperkalaemia if

K+> 6.5 mmol/L● Consider administering sodium bicarbonate (100 mmol) to

correct acidosis if pH < 7.0 (> 100 nmol/L)● Discontinue potentially nephrotoxic drugs and reduce doses

of therapeutic drugs according to level of renal function● Match fluid intake to urine output plus an additional 500 mL● to cover insensible losses once patient is euvolaemic● Measure body weight on a regular basis as a guide to fluid● requirements

Non-renal causes of imbalanced serum urea to creatinine ratio

● Gastrointestinal bleeding● Dehydration● High protein diet (E.g TPN - Total parenteral

nutrition)● High muscle mass● Steroid use● State of metabolic distress (Sepsis)

Chronic Kidney Disease

Patient’s detailsInitials: IARAge: 65Gender: MaleR/N no: HTAN 5008

Chief ComplaintBilateral leg swelling for 2 months

History of Presenting IllnessB/L leg swelling (2 months)

- progressively worsen- no pain, erythema, weakness, numbness

B/L scrotal swelling (1 month)- erythematous- no pain, changes in sensation

Exertional dyspnea (1 month)- duration: less than 5 minutes- relieved upon rest- no cough, URTI symptoms, chest pain, palpitation, sweating, headache, nausea

Increased urinary frequency (5 days)- reduced urine volume- no changes in color or characteristic

Reduced bowel movement (5 days)No abdominal enlargement or pain, no UTI symptoms, no fever

Past Medical History1) gouty arthritis (since 2007)

- affects both big toes- aggravated by peanuts- medications: allopurinol, colchicine

2) h/o urolithiasis (2007)3) renal failure (2007)4) h/o haemodialysis (2007-2012)

- Rt IJC for 8 weeks- Lt AV fistula 2007-2012

5) hypertension (since March 2015)- medication: amlodipine- noncompliant to medication and diet

Family History- mother had CKD- married, has 8 children- son (35 years old) has kidney disease

Social History- works as a rubber tapper- chronic smoker (40 pack years)

stopped 2 years ago- does not consume alcohol or take any drugs- water restriction 800cc/day

noncompliant- noncompliant to hypertensive diet

Physical Examination- alert, conscious, responsive- not in any pain or respiratory distress- I/V cannula attached on left hand

- BP: 188/88mmHgPR: 82 bpm, regular rhythm, strong volumeRR: 17 bpmSpO2: 96%

Chest:- no scars, visible pulsation- apex beat not deviated- S1 S2 heard- no additional heart sounds or

murmurs, no thrills, no heaves

- trachea not deviated- symmetrical chest expansion- bibasal dullness on percussion- increased vocal resonance- vesicular breath sound- bibasal crepitation

Abdomen:- no scars, visible pulsation or

peristalsis- abdomen distended, umbilicus

inverted- soft, non-tender- no hepatomegaly, no splenomegaly- negative fluid thrills and shifting

dullness

Legs:- B/L pedal edema

InvestigationsFBC:Hb: 8.9/dLMCV: 92.6 fLMCH: 31.2 pgWBC: 4.3 x 10^9/Lplatelet: 132 x 10^9/L

Renal Profile:Na: 139 mmol/LK: 5.5 mmol/LUrea: 19.8 mmol/LCr: 662 μmol/L

ABG:pH: 7.38HCO3: 15.4 mmol/L

Medications- T. CaCO3 1.5g TDs- IV lasix 40mg OD- T. allopurinol 150mg OD- T. iberet folate 1/1 OD- T. amlodipine 10mg OD

Pathophysiology and progression of Chronic Kidney Disease

Risk factor related to chronic kidney disease

Risk factor Definition Examples

Susceptibility factors Increase susceptibility to kidney damage Older age, family history of CKD, reduction in kidney mass, low birthweight, US racial or ethnic minority status, low income or education

Initiation factors Directly initiate kidney damage Diabetes, high blood pressure, autoimmune disease, systemic infections, urinary tract infections, urinary stones, lower urinary tract obstruction, drug toxicity

Progression factors Cause worsening kidney damage or faster decline in GFR

Higher level of proteinuria, higher blood pressure, poor glycemic control in diabetes, smoking

End-stage factors Increase morbidity and mortality in kidney failure

Lower dialysis dose, temporary vascular access, anemia, lower serum albumin level, late referral to nephrologists

❏ Possible causes of glomerular scarring and proteinuria:❏ A rise in intraglomerular capillary pressure❏ Increase in glomerular permeability❏ Adaptive glomerular hypertrophy due to reduced

arteriolar and increased glomerular blood flow when there is reduced nephron mass.

❏ Glomerular hyperfiltration, in response to nephron loss, was postulated as a common pathway for the progression of CKD.

❏ Angiotensin II modulates intraglomerular capillary pressure and GFR, causing vasoconstriction of postglomerular arterioles, thereby increasing the glomerular hydraulic pressure and filtration fraction.

❏ Increased intraglomerular capillary pressure causes haemodynamic injury to the capillary wall, resulting in glomerular sclerosis.

❏ Angiotensin II also modulates cell growth by upregulating TGF-β, a potent fibrogenic cytokine, increasing collagen synthesis and causes epithelial cell transdifferentiation to myofibroblast which contributes to matrix formation.

❏ Proteinuria promotes secretion of pro-inflammatory mediators, which promote interstitial inflammatory cell infiltrate and augment fibrosis and progression of CKD.

Complications of ckd

1. Anaemia-Erythropoietin deficiency-Bone marrow toxins retained-Bone marrow fibrosis 2o hyperparathyroidism-Haematinic deficiency-Increased RBC destruction during dialysis-Abnormal RBC membranes-Increased blood loss

2. Renal osteodystrophy-Reduced excretion of phosphates-Release of FGF 23 and other phosphaturic agents by osteoblast-FGF 23 downregulates 1-alpha-hydroxylase and causes phosphaturia-Decreased 1-alpha-hydroxylase reduces activation of vitamin D-Reduced activation and hypocalcemia causes secretion of PTH-Vitamin D required for calcium gut absorption-PTH promotes bone resorption and increased proximal renal tubular reabsorption of calcium-Secondary hyperparathyroidism causes increased osteoclastic activity and bone marrow fibrosis.

3. Pruritus

-due to retention of nitrogenous waste products of protein catabolism

4.Hypertension

Systolic dysfunction due to :-Myocardial fibrosis-Abnormal myocyte function due to uraemia-Calcium overload and hyperparathyroidism-Carnitine and selenium deficiency-Coronary artery calcification

Treatment of CKDThe medical care of patients with CKD should focus on the following:

● Delaying or halting the progression of CKD● Diagnosing and treating the pathologic manifestations of CKD● Timely planning for long-term renal replacement therapy

Delaying or halting the progression of CKD

● Treatment of the underlying conditions● Blood pressure control : ACE Inhibitors or Angiotensin Receptor Blockers● Management of protein : Vitamin D supplementation● Avoiding nephrotoxic drugs including intravenous (IV) radiocontrast media,

nonsteroidal anti-inflammatory agents (NSAIDs), and aminoglycosides

Treating the pathologic manifestations of CKD● Anemia: erythropoietin treatment (Hb level to 10-12 g/dL)● Mineral and bone disorder: phosphate binders (eg, calcium acetate,

sevelamer carbonate, lanthanum carbonate)● Metabolic acidosis: Bicarbonate supplementation● Cardiovascular risk: - statin or statin plus ezetimibe (not for adults with dialysis-dependent CKD)- low-dose of aspirin● Oedema: high doses of loop diuretics(furesomide) with restriction of fluid

and sodium intake.● Restless legs: clonazepam or gabapentin

Renal replacement therapy● Haemodialysis● Haemofiltration● Peritoneal Dialysis● Renal Transplant

Haemodialysis● blood flows on one side of a semipermeable membrane while dialysis fluid

flows in the opposite direction on the other side. ● Solute transfer occurs by diffusion.

Indications: - fluid overload with oliguria- hyperkalaemia- hypercalcaemia- metabolic acidosis- uremic symptoms- GFR <15- acute poisoning

HaemofiltrationPatient's blood is passed through a set of tubing (a filtration circuit) via a machine to a semipermeable membrane(the filter) where waste products and water (collectively called ultrafiltrate) are removed by convection.

Peritoneal DialysisSterile solution containing glucose (called dialysate) is run through a tube into the peritoneal cavity, the abdominal cavity around the intestine, where the peritoneal membrane acts as a partially permeable membrane.

● Continuous ambulatory peritoneal dialysis ( CAPD)

● Automated peritoneal dialysis- Continuous cyclic peritoneal dialysis (CCPD)- Intermittent peritoneal dialysis (IPD)- Night intermittent peritoneal dialysis (NIPD)- Tidal intermittent peritoneal dialysis (TIPD)

Renal Transplant best long-term outcome for patients with end-stage renal disease.

Types of graft:- Cadaveric donor- Non-heart beating donor- Living related donor - Live unrelated donation

Immunosuppressants: cyclosporin, azathioprine, prednisolone , pre-op anti-interleukin 2 receptor antibodies (basiliximab)

Contraindications: cancer, active infections, uncontrolled ischaemic heart disease, acquired immunodeficiency disease with opportunistic infections, active viral hepatitis ,extensive peripheral vascular disease, mental incapacity.

RRT ComparisonHemodialysis Peritoneal Dialysis Renal Transplant

Pros ● Cheaper ● More freedom, can be done at home

● Greater liberty from dietary restrictions

● Easily tolerable by patients with poor cardiac reserve

● No vascular access● Conserves residual kidney

function

● Restores kidney function completely (for 10-15 years)

Cons ● Frequent traveling to dialysis centre

● Needs to be on anticoagulants● (risk of thrombosis)● AV fistula for vascular access -

may collapse/risk of infection● Hypotension● Dietary restrictions

● Risk of peritonitis● Needs to be disciplined and

knowledgeable in handling dialysis

● Costly

● Long waiting list● Extremely costly● Risk of organ rejection● Need to be on

immunosuppressants● Need to undergo second

transplant after transplanted kidney fails

Urinary Tract Infections (UTI)

Urinary Tract Infections (UTI)Most commonly : Escherichia coli species (80-90% of cases) Other causes : Klebsiella, Enterococcus, Proteus mirabilis and Staphylococcus saprophyticus.Most of the causative organisms are naturally present in the GI tract, which acts as a natural reservoir for potential UTIsMajor defense against UTI : complete emptying of the bladder during urination. Other mechanisms : urine acidity, vesicoureteral valve, and various immunologic and mucosal barriers.Spread via: 95% Ascension5% Haematogenous

Symptoms and signs of UTI● Frequency of micturition● Dysuria● Suprapubic pain & tenderness● Haematuria● Smelly urine● Loin pain & tenderness● Fever & systemic upset（chills, rigors, flank pain, colicky abdominal pain, nausea, vomiting）

Pyelonephritis

Cystitis

Investigations & TreatmentIx:

Urinalysis (clean-catch, midstream specimen)

● Microscopic examination of urine : > 10 WBCs/μL

● Dipstick tests

Urine culture

● Culture criteria for symptomatic patients : Uncomplicated cystitis in women: > 10 3 /mL

Complicated UTI: > 10 5 /mLTx:Antibiotics: Amoxicillin/trimethoprim/cephalosporin (if resistance, co-amoxiclav(Augmentin)/

ciprofloxacin)

Acute Kidney Injury VS Chronic Kidney Disease

Acute Kidney Injury Chronic Kidney Failure

Progression* Rapid progressive loss of renal function

Gradual loss of renal function

Onset & Duration of symptoms* Acute, Hours to Days Gradual, >3 months

Symptoms Oliguria, Edema (Fluid overload), Arrhythmia (↑ K+) , metabolic acidosis (Unable to form HCO3-).

Oliguria/Anuria + Renal osteodystrophy*, Anemia*, Edema (fluid overload), mild metabolic acidosis, pruritus (cutaneous urea deposition

Anemia Possible due to pathological cause of AKI e.g Haemorrhage

Normochromic, normocytic Present due to ↓ erythropoetin production

Osteodystrophy Absent Present

Serum Calcium & Phosphate Normal Increased phosphate, decreased calcium(Increased calcium in secondary hyperparathyroidism

USG Enlarged kidneys Shrunken Kidneys/ Normal (PKD)