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Disorders of the Kidney and Urinary Tract

Acute Kidney Injury
Definition - Impaired kidney filtration and excretion over days to weeks resulting in
o Serum creatinine
o Urine volume
- With or without injury to the renal parenchyma
Epidemiology - 30% of ICU cases → 50% mortality rate
- Community acquired
o Volume depletion, heart failure, ADR of medications, UTO, malignancy
- Hospital acquired
o Sepsis, major surgical procedures, heart or liver failure, nephrotoxic medication
administration
- Infectious causes
o Malaria, leptospirosis
Classification
overview

Etiology and Prerenal Azotemia

Pathophysiology - Most common as a renal perfusion to support normal GFR
- No parenchymal damage and is reversible once BF is restored
- Common clinical conditions
o Hypovolemia
o CO
o Medications
▪ NSAIDs: constrict afferent arterioles
▪ ACEI and ARBs: dilate efferent arterioles
- Prolonged → ischemic injury (ATN)
- Responses to maintain GFR in response to effective circulating volume
o Angiotensin II: efferent vasoconstriction
o Norepinephrine
o Vasopressin (ADH)
o Myogenic reflex within afferent arterioles → dilation by PG, NO synthesis
o Tubulo-glomerular feedback
▪ Decreased solute delivery to macula densa → dilation of afferent arteriole
Intrinsic AKI
- Most common causes
o Sepsis
o Ischemia
o Nephrotoxins (endo and exogenous)
1. Sepsis-associated AKI
- Generalized vasodilation → GFR → RAAS activation →excessive vasoconstriction
- Endothelial damage → leukocyte adhesion and migration → thrombosis, permeability,
interstitial pressure, tubular BF, ROS activation → tubular injury → casts and debris in
the urine
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2. Ischemia-associated AKI
- In the context of CKD or older age (limited renal reserve), sepsis, nephrotoxic drugs,
rhabdomyolysis, burns, pancreatitis
- Continuation of prerenal azotemia
o Postoperative
o Pancreatitis
o Burns
o Diseases of microvasculature
▪ Thrombotic microangiopathies
• TTP/HUS
• Scleroderma
• Atheroembolic disease
• Malignant HTNsive nephrosclerosis
• Radiation and CTX agents, cocaine
• Antiphospholipid antibody syndrome
▪ Large-vessel associated
• Renal artery dissection, thromboembolism, or thrombosis
• Renal vein compression or thrombosis
3. Nephrotoxin-associated AKI
- Nephrotoxins
o Contrast agents
o Antibiotics: vancomycin, aminoglycosides
o CTX agents: cisplatin, carboplatin
o Toxic ingestions
o Endogenous toxins: myoglobin, hemoglobin, uric acid, myeloma light chains
o Others: NSAIDs, PPIs, Sarcoidosis
- AKI 2ndary to AIN can be due to
o Penicillin, cephalosporins, rifampin, sulfonamides
 Aminoglycosides cause non-oliguric AKI
4. Glomerulonephritis (5% of AKI)
- Involve glomerular podocytes, mesangial and endothelial cells
- Compromise filtration barrier and BF within real circulation
Postrenal AKI
- Bilateral obstruction or unilateral in severe CKD or unilateral kidney
Etiologies
- BPH or prostate cancer
- Neurogenic bladder
- Blood clots, calculi, urethra strictures
- Ureteric obstruction
- Infiltration of ureters by malignancy
- External compression: retroperitoneal fibrosis, neoplasia, abscess
Diagnostic - SCr >0.3mg/dl within 48 h
Evaluation - 50% from baseline within 1 week
- UOP to <0.5mL/kg per h for longer than 6 h
AKI vs CKD
- Small shrunken kidneys with cortical thinning
- Evidence of renal osteodystrophy
- Normocytic anemia in the absence of blood loss
- 2ndary hyperPTH + hyperphosphatemia + hypocalcemia
Hx and P/E Prerenal
- Hx: VD, diuretics, NSAIDs, ACEIs, ARBs
- P/E: orthostatic hypotension, tachycardia, JVP and skin turgor
- Comorbidities: CHF, liver disease, nephrotic syndrome
Postrenal
- Hx: prostatic disease, nephrolithiasis, pelvic or paraaortic malignancy, colicky flank pain,
nocturia, hesitancy, frequency
- P/E: abdominal fullness and suprapubic pain due to bladder enlargement
Intrinsic
- Hx:
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o medications + dosage, allergic IN (fever, arthralgia, pruritic erythematous rash)

o Hx of AID such as SLE may be due to worsening of the underlying disease
o Pregnancy: preeclampsia
- Systemic vasculitis w GN: palpable purpura, pulmonary hemorrhage, sinusitis
- P/E: tense abdomen – compartment syndrome, limb ischemia – rhabdomyolysis
Urine findings - Non-Oliguric AKI
o Nephrogenic diabetes insipidus due to long standing urinary tract obstruction
o Tubulointerstitial disease
o Nephrotoxicity from cisplatin or aminoglycosides
- Red or brown urine
o Rhabdomyolysis or hemolysis
- Nephrotic range proteinuria >3.5gm/day
o GN
o Vasculitis
o Toxins/medications such as NSAIDs
- Casts
o Hyaline: pre-renal azotemia
o Muddy brown: ATN
o WBC cast: Interstitial nephritis
- Eosinophils
o AIN, pyelonephritis, cystitis, Atheroembolic disease, GN
- Oxalate crystals: ethylene glycol toxicity
- Uric acid crystals: tumor lysis syndrome
Lab findings - CBC
o Anemia
▪ Hemolysis, multiple myeloma, thrombotic microangiopathies (HUS/TTP)
o Eosinophilia
▪ Interstitial nephritis, polyarteritis nodosa, Churg-Strauss vasculitis
o Thrombocytopenia
▪ TTP/HUS
- ADAMTS13 (VWF cleaving protease) and Shiga toxin for HUS
- Electrolytes
o Hyperkalemia
o Hyperphosphatemia
o Hypocalcemia
- For GN and Vasculitis
o complement
o ANA
o Anti-GBM
o ANCA
o Cryoglobulins
Urine Indices

Complications 1. Uremia - In rhabdomyolysis, hemolysis, tumor lysis

- Mental status changes syndrome
- Bleeding complications - Can lead to arrhythmias
2. Hyper and hypovolemia 6. Bleeding
- Edema: weight gain, pulmonary edema - Can lead to anemia
- Polyuria during recovery - Due to AKI related uremia →
3. Hyponatremia erythropoiesis and platelet dysfunction
- Can lead to seizures 7. Cardiac complications
4. Acidosis - Arrhythmias, pericarditis, pericardial
5. Hyperkalemia effusion
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Glomerular Diseases
Acute GN - Azotemia + HTN + edema + hematuria + proteinuria + oliguria
- RBC casts on urinalysis
- Proteinuria usually <3g/ds
Acute Poststreptococcal GN
- Most common in pediatrics: 1-3wks after pharyngeal or cutaneous infection with GAS
- ASO, Anti-DNase positive, proliferative GN on biopsy
Post infectious GN
- Following bacterial, viral or parasitic infections
o Bacterial endocarditis, sepsis, HBV, pneumococcal pneumonia
Rapidly - GFR by 50% + evidence of proliferative GN
Progressive GN Classification
1. Immune complex associated: SLE
- SSx: rash, serositis, alopecia, CNS disease
- Lab: ANA, anti-dsDNA, complements
2. Pauci-immune: associated with ANCA
- Systemic vasculitis such as Wegner’s or Granulomatosis with polyangiitis, microscopic
polyangiitis, Churg-Strauss syndrome
- There is circulating ANCA (cytoplasmic and perinuclear) in small vessels and glomerular
capillaries
- SSx: prodromal flulike syndrome with myalgia, fever, arthralgia, anorexia, and weight loss
- Tx: plasmapheresis
3. Anti GBM associated: Goodpasture’s syndrome
- Young M and older M and F
- Focal or segmental necrosis on biopsy → crescent formation → interstitial nephritis +
fibrosis and tubular atrophy
Henoch-Schoenlein Purpura
- Generalized vasculitis → IgA nephropathy, purpura, arthralgias and abdominal pain mainly
in children
- Hematuria and proteinuria is present + IgA
Nephrotic - Albuminuria >3.5g/d + hypoalbuminemia <30g/L + edema + hyperlipidemia + lipiduria
Syndrome - Diabetes is the most common cause in adults
- Complications: renal vein thrombosis, thromboembolic events, infection, Vitamin D
deficiency, protein malnutrition, drug toxicities
Minimal Change disease
- Most common cause of NS in children
- Responds to steroids, selective albuminuria
- Etiologies, recent URTI, allergies, NSAIDs
Membranous GN
- IgG deposits + edema + proteinuria
- + renal vein thrombosis, circulating antibodies
Focal glomerulosclerosis
- Primary
o Acute, + HTN, renal insufficiency + hematuria
o Fibrosis of juxtamedullary glomeruli
o HIVAN
- Secondary
o Late stages of any form of kidney diseases
Membranoproliferative GN
- C3 deposition in granular pattern
- Linked to HCV infection associated to cryoglobulinemia
Diabetic Nephropathy
- Most common cause of NS
- GBM thickening, mesangial sclerosis, arteriosclerosis
- Kimmelstiel-Wilson nodules
Tubular Disease
AIN - Drugs are leading cause
- SSx: Fever, eosinophilia + rash + arthralgia
- Azotemia + tubular dysfunction
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- Urinalysis: Hematuria + pyuria + WBC casts, eosinophiluria

Overview
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Anemia Overview
Normal Values

Classification

Clinical - Postural hypotension, tachycardia

presentation - >40% - hypovolemic shock, confusion, dyspnea, diaphoresis, hypotension, tachycardia
- IV hemolysis: back pain, hb in plasma and urine, renal failure
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Otherwise Statements
- No hx of SOB, orthopnea, PND, palpitation (CHF)
- No hx of yellowish discoloration of the skin, eye (hepatic cause)
- No hx of strangury, dribbling, urgency, hesitancy (postrenal)
- No hx of cough, hemoptysis, myalgia (Good posture syndrome)
- No hx of diarrhea, weight loss (protein losing enteropathy)
- No hx of sore throat, skin rash, URTI (post strep GN)
- No hx of any prior drugs like NSAIDS, antibiotic (prerenal)
- No hx of headache, loss of consciousness, abnormal body movement (uremic
encephalopathy)
- No hx of blurred vision, tinnitus, lightheadedness (Anemia)
- No hx of trauma, radiation exposure, or surgery (ATN)
- No hx of cellulitis, skin purpura, abdominal cramp (IgA nephropathy)
- No hx of smoking, alcohol or other drug abuse (atherosclerosis prerenal)
- No hx of similar illness in the past or family hx of DM, heart and kidney disease
- No hx of contact with river water (schistosomiasis)
- No hx abnormal body movement, joint pain, subcutaneous nodules (IE)
- No hx of rash around sun exposed area of the face, joint pain, fever (SLE)
- No hx of blood transfusion, multiple sexual partners, iv drug abuse
- No hx of fever, bleeding tendency, change in mood/behavior (TTP/HUS)
- No hx of cold intolerance, hair loss, weight gain despite normal appetite (hypothyroidism)
- No hx of travel to malaria endemic region
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