Genitourinary Renal System
Acute Kidney Injury (AKI) and Related Renal Conditions
AKI definition: abrupt or rapid decline in kidney function resulting in waste retention and dysregulation of volume status and electrolytes; often prerenal causes and acute tubular necrosis (ATN) are most common etiologies; KDIGO staging defines AKI and its criteria.
KDIGO AKI criteria:
Increase in serum creatinine by at least 0.3\,\text{mg/dL} within 48 hours, or
Increase in serum creatinine by at least \geq 1.5\times baseline within the prior 7 days, or
Urine volume < 0.5\,\text{mL/kg/hr} for 6 hours.
Typical AKI course: may last about 7-21\text{ days}; some recover in days, others require dialysis for months.
Common etiologies and categories:
Prerenal (hypoperfusion) due to volume depletion, decreased cardiac output, or renal hypoperfusion states; often reversible with rehydration.
Intrarenal (ATN, acute interstitial nephritis, glomerular disease) involving parenchyma or tubules; ATN causes ~90% of intrinsic AKI and is often reversible.
Postrenal (obstruction) due to bladder outlet or ureteral/renal obstruction; bilateral obstruction or single kidney with obstruction can cause AKI.
KDIGO staging for AKI is distinct from CKD staging and guides management and prognosis.
Normal Findings: Kidneys and Urinary System
Location: retroperitoneal; right kidney sits lower than left due to liver displacement.
Basic functional units: nephrons (contain glomeruli).
Kidney roles:
Regulate electrolytes and fluids to influence blood pressure.
Water reabsorption influenced by antidiuretic hormone (ADH) and aldosterone.
Excretion of water-soluble wastes (e.g., creatinine, urea, uric acid).
Hormone secretion:
Erythropoietin (RBC production)
Renin and bradykinin (blood pressure)
Prostaglandins (renal perfusion)
Calcitriol (vitamin D3) for bone health
Average daily urine output: \approx 1500\,\text{mL}.
Oliguria definition: urine output < 400-500\,\text{mL/day} in adults.
Laboratory Testing: Key Markers and Indices
Serum Creatinine
Creatinine source: product of creatine metabolism in skeletal muscle and from dietary meat intake.
Normal values differ by sex due to muscle mass:
Males: 0.7-1.3\,\text{mg/dL}
Females: 0.6-1.1\,\text{mg/dL}
When renal function declines, serum creatinine rises; creatinine may be falsely low with low muscle mass (e.g., older adults).
Serum creatinine levels vary inversely with GFR.
Creatinine Clearance (24-hour urine)
Used to evaluate proteinuria/albuminuria/microalbuminuria and to reflect renal function over a 24-hour period.
Characteristics:
More sensitive than serum creatinine alone for certain assessments.
Relatively constant and not affected by fluid status, diet, or exercise.
Creatinine clearance roughly doubles for every 50% reduction in GFR.
Practical note: ideally, exercise should be avoided immediately before and during specimen collection.
Estimated Glomerular Filtration Rate (eGFR)
eGFR is the best overall test to measure kidney function and to stage CKD (per KDIGO).
Normal eGFR: >90\,\text{mL/min}.
CKD defined as eGFR < 60 for at least 3 months (with or without kidney damage).
eGFR calculation:
Based on serum creatinine, age, and sex.
Two common equations used historically: Modification of Diet in Renal Disease (MDRD) and CKD-EPI (2009).
2021 CKD-EPI equation is now recommended and was developed without a race coefficient.
GFR factors:
Age-related decline with age
Sex differences due to muscle mass
Body size
Some patients with underlying kidney disease may have a normal eGFR; eGFR can be less reliable in pregnancy, muscle wasting, elderly patients, and lower-extremity amputees.
Tips:
eGFR is considered the best overall measure of renal function in primary care.
Serum creatinine is a better measure of renal function than BUN or BUN/Cr ratio for many purposes.
Blood Urea Nitrogen (BUN)
BUN reflects the liver's conversion of amino acids to ammonia, than urea; assesses kidneys’ ability to excrete urea.
BUN can rise with kidney damage or decreased renal blood flow; it is less sensitive than creatinine or eGFR.
Urea production is not constant—can increase with high-protein diet, tissue breakdown (hemorrhage, trauma, glucocorticoids).
Low-protein diet or liver disease can lower BUN without affecting GFR.
In heart failure, lower GFR with higher BUN correlates with higher mortality; in ICU, elevated BUN is independently associated with mortality.
BUN-to-Creatinine Ratio (BUN:Cr)
A rise in the BUN:Cr ratio suggests decreased kidney perfusion (prerenal state).
Used to help classify prerenal, infrarenal, or postrenal etiologies of AKI.
Urinalysis (UA) with Microscopic Exam
A complete UA includes gross evaluation, dipstick analysis, and microscopic urine sediment.
Epithelial cells:
Large amounts of squamous epithelial cells indicate contamination (normal to have a few).
Squamous cells from external urethra; transitional epithelial cells from the bladder.
White Blood Cells (Leukocytes):
Normal WBCs in urine: ≤2-5 WBCs/hpf (high-power field).
Leukocyte esterase indicates presence of WBCs.
Presence of neutrophils commonly associated with bacteria.
Leukocytes in urine (pyuria) almost always present in acute cystitis in males.
Red Blood Cells:
Few RBCs (<3 cells) considered normal.
Microscopic hematuria = RBCs visible only on microscopy.
Gross hematuria = visible blood in urine; color ranges pink/red/cola/brown; bleeding may originate from urethra (urethritis), bladder (cystitis or cancer), or kidneys (stones, pyelonephritis, PKD, cancer).
Contamination possible from menses, vaginal discharge, semen, hemorrhoids, rectal bleeding.
Protein:
Persistent protein suggests chronic kidney damage; assess serum creatinine and eGFR; request urine for microscopy.
Isolated proteinuria = proteinuria with normal kidney function and stable sediment.
Transient proteinuria common in patients ≤18 years or young adults; diagnosed if repeat test becomes negative.
Benign causes include fever, intense physical activity, acute illness, dehydration, emotional stress; may be present in acute pyelonephritis (resolves after treatment).
Urine dipsticks are sensitive to albumin; false positives can occur with alkaline urine (pH > 7.5), excessive immersion, concentrated urine, gross hematuria, semen, or vaginal secretions.
For quantification, order 24-hour urine protein or protein-to-creatinine ratio (UPr/Cr).
Nitrites:
Bacteria reduce urinary nitrate to nitrite; positive nitrite is highly indicative of a UTI.
Casts:
Cylindrical structures formed in renal tubules.
Hyaline casts: nonspecific; seen with low urine volumes or diuretic therapy.
Granular casts: protein or other debris suggestive of infection or inflammation.
WBC casts: seen with infection (pyelonephritis) or interstitial nephritis.
RBC casts: suggest glomerular bleeding (glomerulonephritis) with edema, dark urine, hypertension.
Urine pH:
Reference range: 4.5 to 8.0; useful for evaluating stones and infections.
Diet effects: citrus/low-carb diets lower acidity; high-protein diets raise acidity.
Urine Culture and Sensitivity (C&S):
Confirms bacteriuria and identifies antibiotic susceptibility.
Specimen: clean-catch voided sample for suspected UTI.
Positive culture: ≥ 10^5 CFU/mL of one dominant organism.
If multiple organisms: sample may be contaminated; lower values may still indicate bacteriuria.
Tips:
Interpret UA results in the context of UTI.
WBC casts with proteinuria and hematuria are associated with pyelonephritis.
Chronic Kidney Disease (CKD) Stages
Stage I: GFR \ge 90 mL/min; Kidney damage with normal or high kidney function.
Stage II: GFR 60-89 mL/min; Mild loss of kidney function.
Stage IIIa: GFR 45-59; Mild-to-moderate loss.
Stage IIIb: GFR 30-44; Moderate-to-severe loss.
Stage IV: GFR 15-29; Severe loss.
Stage V: GFR < 15 mL/min; Kidney failure.
Acute Kidney Injury: Causes, Staging, and Management
AKI is an abrupt reduction in GFR with waste retention and electrolyte/volume dysregulation.
Common presentations include oliguria, edema, weight gain, lethargy, nausea, malaise.
KDIGO AKI staging criteria (as above) are used to define and stage AKI.
Pre-renal causes: due to hypoperfusion
Intrinsic renal causes: include ATN, nephrotoxic drugs, glomerular diseases; ATN accounts for the majority of intrinsic AKI and is often reversible.
Post-renal causes: obstruction within the urinary tract; obstruction commonly bilateral or in a patient with single functioning kidney.
General management:
Early nephrology and ED referral when indicated.
Dialysis emergently for hypervolemia with pulmonary edema, severe hyperkalemia, life-threatening uremic symptoms, or toxin exposure.
Remove nephrotoxic insults, correct hypovolemia, correct electrolyte abnormalities and acidosis, provide nutrition management (potassium, phosphorus, fluid limits).
Nephrotoxic drugs include (examples):
Acyclovir, allopurinol, aminoglycosides, certain antivirals, beta-lactams, chemotherapy agents, contrast dyes, diuretics, illicit drugs, lithium, NSAIDs/analgesics, proton pump inhibitors, quinolones, sulfonamides, and others.
AKI etiologies by category (summary):
Pre-renal: hypovolemia, decreased cardiac output, third-space sequestration (sepsis, pancreatitis, hypoalbuminemia), medications limiting GFR (ACE inhibitors, ARBs, NSAIDs).
Post-renal: bladder obstruction (BPH, cancer), urethral/renal obstruction (stones, strictures, clots, cancer), neurogenic bladder.
Intra-renal: ATN (ischemia/hypoperfusion/sepsis/hemorrhage/nephrotoxins); drugs such as NSAIDs, diuretics, penicillins, cephalosporins, sulfa drugs, allopurinol, anticoagulants; glomerular diseases; thrombosis of renal vessels.
Acute Pyelonephritis
Acute bacterial infection of the kidneys; most commonly caused by gram-negative Enterobacteriaceae (E. coli 75-95%, Proteus, Klebsiella).
Outpatient treatment suitable for compliant, healthy patients with milder disease (uncomplicated):
Oral fluoroquinolones (e.g., levofloxacin or ciprofloxacin) for 5-7 days.
Complicated/Severe disease or immunocompromised patients require hospitalization for rehydration and management of complications; refer for inpatient care.
Classic case: high fever, chills, anorexia, nausea/vomiting, unilateral flank pain; may have cystitis symptoms (dysuria, frequency, urgency).
Diagnostic criteria and tests:
Temperature ≥ 100.4\,\text{°F} (≥ 38.0 °C)
Costovertebral angle tenderness
Urinalysis: leukocytes, hematuria, nitrites, mild proteinuria
Urine casts: WBC casts on microscopic exam
Urine culture and sensitivity: ≥ 10^5\,\text{CFU/mL} of one organism
CBC: leukocytosis, neutrophilia with left shift (bands) suggesting infection
Chemistry panel including serum creatinine
Pregnancy, children/elderly, male patients, kidney stones, anatomic abnormalities, diabetes, and immunocompromise require specialist referral.
Management tips:
Distinguish classic acute simple cystitis vs. acute pyelonephritis.
Monitor for progression to bacteremia/sepsis, and adjust therapy if needed.
Asymptomatic Bacteriuria (ASB)
Defined as presence of one or more bacterial species in urine at ≥ 10^5\,\text{CFU/mL} without UTI symptoms.
Prevalence:
Healthy females: increases with age, from ~1% to >20% after age 80.
Diabetics: 8-14% prevalence.
Males >75 years: 6-15%.
Treatment indications:
Pregnancy, patients undergoing urologic intervention, renal transplant recipients.
Screening/treatment not recommended for older patients, diabetics, indwelling catheters, or those undergoing non-urologic surgery.
Chronic Kidney Disease (CKD) Overview
CKD definition: presence of kidney damage (structural or functional abnormalities) or GFR <60ml/min/1.73for 3+ months, regardless of cause.
Common etiologies: poorly controlled diabetes mellitus and hypertension.
CKD staging is based on GFR.
Classic CKD presentation: edema from fluid overload or hypertension; fatigue, weakness, anorexia, vomiting, pruritus; advanced disease may cause encephalopathy or seizures.
Physical findings:
Volume overload: weight gain, edema, shortness of breath
Volume depletion signs in other contexts: fatigue, postural dizziness, tachycardia, dry skin
Possible findings: rashes, skin lesions, abnormal bruits or distal pulses (renal artery stenosis), enlarged kidneys (polycystic disease), peripheral neuropathy with diabetic disease
Laboratory features:
Serum creatinine and BUN often elevated; eGFR decreased; proteinuria/albuminuria may be present on urine microscopy
CBC may show anemia; metabolic derangements such as hyperkalemia, hyperphosphatemia, metabolic acidosis, hypocalcemia, elevated PTH
Urine studies may show proteinuria/albuminuria and possibly RBCs/WBCs
Random protein-to-creatinine ratio and albumin-to-creatinine ratio quantify protein/albuminuria
Diagnostics:
CBC with differential
Basic metabolic panel
Urinalysis with microscopy
Kidney ultrasound to assess structural abnormalities; vascular duplex ultrasound to evaluate renal artery stenosis
Management:
May require dialysis in some patients; trajectory and duration determine therapy needs
Nephrology consult for advanced disease (eGFR <30mL/min/1.73, persistent high proteinuria, etc.)
Diet and education:
Nutritional support tailored to eGFR and comorbidities; DASH diet is a common reference diet for renal patients
Hematuria: Types, Evaluation, and Implications
Two types:
Microscopic hematuria: RBCs detectable only on microscopy (≥3 RBCs/hpf sometimes used as threshold)
Gross (visible) hematuria: pink/red/brown urine; may contain clots
Possible sources include urethra, bladder, prostate, kidneys (pyelonephritis, stones, cancer, PKD)
Diagnostic approach:
UA with microscopy; if infection suspected, assess leukocytes and nitrites
Consider urine cytology if urothelial malignancy suspected (risk factors include age >50, male sex, smoker, gross hematuria)
In gross hematuria with clots or persistent bleeding, imaging and nephrology/urology referral
Post-infectious hematuria considerations: new dark urine after strep infection suggests possible poststreptococcal glomerulonephritis (PSGN), common in children; onset 10 days to 3 weeks after infection
Glomerular and Renal Bleeding Syndromes
Glomerular bleeding may yield gross hematuria without clots; consider glomerulonephritis.
Hematuria workup may include imaging and nephrology referral when glomerular disease is suspected.
Nephrolithiasis (Renal Calculi)
Stone composition:
Calcium oxalate: 70-80%
Calcium phosphate: ~15%
Struvite: ~1%
Uric acid: ~8%
Cystine: 1-2%
More common in males; prevalence increases with age.
Pain presentation depends on stone location and size; renal pelvis or upper tract stones cause flank pain; distal stones cause abdominal pain and may radiate to genitals.
Risk factors for calcium stones:
Urinary factors: low volume, high calcium, high oxalate, low citrate, high urine pH
Anatomic: horseshoe kidney, medullary sponge kidney
Diet: high calcium/oxalate, high sodium and protein intake, low fluids, high sucrose/fructose
Other conditions: obesity, diabetes, gout, IBD, post-bariatric surgery
Non-modifiable: family history, genetics, White race
Classic case: sudden colicky flank pain on one side with waves; may have nausea/vomiting; most stones pass spontaneously within 48 hours in many cases; gross or microscopic hematuria common.
Diagnostics:
UA often shows hematuria; microscopy may show crystals depending on stone type
CT abdomen/pelvis without contrast is the preferred imaging modality; ultrasound alternatives in pregnancy or if CT unavailable
Management:
Most stones managed conservatively with analgesia and hydration if the patient tolerates PO intake and fluids
Stones ≤ 5 mm largely pass spontaneously; advise patient to strain urine and bring passed stone for analysis
Stones 5-10 mm: consider tamsulosin (or other alpha-blocker) for up to 4 weeks to facilitate passage; calcium channel blockers may also be used
Pain control: NSAIDs (e.g., indomethacin, ketorolac) and/or opioids; NSAIDs may reduce ureteral spasm but can worsen AKI risk in dehydration or CKD
Stones > 10 mm or failed medical expulsive therapy, urology consult; larger stones may require ESWL (extracorporeal shock wave lithotripsy) or other interventions
Indications for ED referral include fever (possible urosepsis), persistent severe pain, AKI, anuria, inability to tolerate oral medications, or large stones
Diet and prevention:
Increase fluids to 2-3 L/day
For calcium oxalate stones, limit high-oxalate foods (rhubarb, spinach, okra, nuts, beets, chocolate, tea, some meats)
Proteinuria: Types, Evaluation, and Implications
Definition: excretion of >150\,\text{mg/day} of protein.
Proteinuria as a marker of kidney damage; persistent proteinuria warrants etiologic investigation.
Four major types:
Glomerular, tubular, overflow, postrenal
Assessment:
Gold standard: 24-hour urine collection for protein excretion
Urine dipstick detects albumin poorly at low levels; microalbuminuria may be missed without concentration; repeat testing may be needed.
Transient proteinuria: common in fever, exercise, acute illness, dehydration, emotional stress; if transient, repeat test may be negative.
False positives and confounders: fever, dehydration, etc., may affect results; persistent or significant proteinuria requires further workup.
Urinary Tract Infections (UTIs)
Cystitis (bladder inflammation) can be uncomplicated, recurrent, reinfection, or relapse; most UTIs are due to Enterobacteriaceae (E. coli, Klebsiella, etc.).
Common pathogens and risk groups:
Infants: UTIs common in boys in first 6 months due to anatomical issues.
Children: UTIs require evaluation; ~2.5% of children get a UTI; may indicate vesicoureteral reflux or risk of abuse.
Females: Highest incidence during reproductive years.
Older females: New urinary symptoms or incontinence can indicate UTI.
Risk factors:
Female sex, pregnancy, recent UTI history, diabetes/immunocompromised, postcoital UTI, poor hydration, catheterization, use of spermicides (nonoxynol-9) increasing risk of UTIs.
Classic female UTI case: dysuria, frequency, urgency, nocturia; suprapubic discomfort; UA shows leukocytes and nitrites; urine culture may be positive.
Diagnosis and testing:
UA dipstick: leukocyte esterase; nitrites; WBCs; hematuria; pH; possibly protein.
Urine culture (C&S): commonly >= 10^5\,\text{CFU/mL} of a single organism; mixed flora may indicate contamination.
In uncomplicated cystitis in healthy females, UA alone may suffice; C&S not routinely required.
Acute simple cystitis in healthy adult females (outpatients): First-line antibiotics include
Nitrofurantoin 100\,\text{mg} twice daily for 5\text{ days}; trimethoprim-sulfamethoxazole (TMP-SMX) 160/800\,\text{mg} twice daily for 3\text{ days}; fosfomycin single dose 3\,\text{g}; pivmecillinam 400 mg orally three times daily for 3-5 days (some guidelines vary by region).
Special considerations:
For patients at risk of resistant organisms, options include nitrofurantoin, fosfomycin, pivmecillinam; fluoroquinolones may be used in certain resistant cases but have higher risk of resistance and adverse effects.
Phenazopyridine (Pyridium) is a urinary analgesic for symptomatic relief; it colors urine orange and can stain contact lenses; avoid in liver/kidney disease or G6PD deficiency; not curative.
Fluid intake: increase to 2-3 L/day; dietary oxalate restriction advised in stone-formers, not specifically required for all simple cystitis.
Recurrent UTIs in females:
Defined as three or more culture-positive UTIs in 1 year or two UTIs within 6 months.
Antibiotic prophylaxis is not first-line therapy.
Postcoital prophylaxis options include nitrofurantoin, TMP-SMX, cephalexin; advise hydration and avoid spermicides; estrogen therapy may be used in postmenopausal women; cranberry products and probiotics lack demonstrated efficacy.
Acute simple cystitis in adult males:
Less common; evaluate for underlying structural issues (urethral stricture, BPH, calculi, uncircumcised status).
Management similar to females but with broader differential including STI testing (NAAT for gonorrhea and chlamydia).
Pearls and cautions:
Do not routinely screen or treat ASB in most populations except indicated groups (e.g., pregnancy).
Avoid prolonged nitrofurantoin use due to risk of lung, hepatic, and neuropathic toxicity; monitor in patients with CKD.
ACE inhibitors/ARBs require potassium monitoring in patients with CKD due to risk of hyperkalemia.
Contrast media can cause contrast-associated AKI; higher risk in CKD or diabetes; minimize exposure when possible.
Acute Simple Cystitis in Males and Special Considerations
In adult males, assess for structural/anatomic causes (urethral stricture, BPH, stones, uncircumcised) and potential STI involvement; treat with nitrofurantoin, TMP-SMX, or fosfomycin as appropriate; evaluate for recurrent infections and refer to urology if needed.
Long-term nitrofurantoin use is associated with lung problems, chronic hepatitis, and neuropathy; baseline tests (chest X-ray, LFTs) and monitoring advised; contraindicated in renal insufficiency.
Urinary Tract Imaging and Procedures
Imaging preferences:
Noncontrast CT scan is the highest sensitivity/specificity for kidney stones.
Ultrasound can be used when CT is unavailable or if patient is pregnant.
Urine cytology and cystoscopy considerations in suspected malignancy or persistent hematuria with risk factors.
Practical Tips and Educational Highlights
eGFR is the best single measure of renal function in primary care; use eGFR for CKD staging and progression monitoring.
Serum creatinine alone can be misleading in certain populations (older adults, low muscle mass); use eGFR and creatinine clearance when appropriate.
BUN/Cr ratio helps classify prerenal vs intrinsic renal disease and guides management.
Urinalysis interpretation should consider contamination, pyuria, nitrite positivity, leukocyte esterase, casts, and hematuria patterns to differentiate UTI, pyelonephritis, and glomerular/glomerulonephritis processes.
In AKI, rapid identification of prerenal causes and avoidance of nephrotoxins are essential, followed by careful fluid and electrolyte management.
For stone prevention, appropriate hydration and dietary modifications depend on stone type; oxalate-rich foods should be moderated for calcium oxalate stones.
DASH diet is a common dietary framework for CKD-related nutrition planning; nutrition should be individualized based on eGFR and comorbidities.
Education on recognizing symptoms, appropriate timing of imaging, and when to seek ED or specialist care is critical for AKI and CKD management.
Equations and Numerical References (LaTeX)
KDIGO AKI criteria:
\Delta Cr \ge 0.3\,\text{mg/dL} \text{within } 48\text{ hours}
\Delta Cr \ge 1.5 \times \text{baseline within 7 days}
\text{Urine output} < 0.5\,\frac{\text{mL}}{\text{kg}\cdot \text{hr}} \text{for } 6\text{ hours}
eGFR normal threshold: \text{eGFR} > 90\,\text{mL/min}
CKD staging GFR cutoffs:
Stage I: \text{GFR} \ge 90\quad\text{mL/min} (kidney damage with normal/high function)
Stage II: 60 \le \text{GFR} \le 89\quad\text{mL/min}
Stage IIIa: 45 \le \text{GFR} \le 59\quad\text{mL/min}
Stage IIIb: 30 \le \text{GFR} \le 44\quad\text{mL/min}
Stage IV: 15 \le \text{GFR} \le 29\quad\text{mL/min}
Stage V: \text{GFR} < 15\quad\text{mL/min}
Urine culture thresholds:
Positive culture: \ge 10^5\ \text{CFU/mL} of one dominant organism.
Proteinuria threshold (excretion):
> 150\ \text{mg/day} of protein.
References to Clinical Scenarios and Tables (Conceptual)
Classic cases described throughout the notes illustrate AKI, AKI etiologies, pyelonephritis, CKD progression, ASB management, UTI management, nephrolithiasis management, and urinary laboratory interpretation.
Use based on KDIGO definitions, eGFR-based CKD staging, and guideline-consistent antibiotic options for uncomplicated cystitis and pyelonephritis, with attention to resistance risks and patient comorbidities.