Nephrology and Urology Notes

Renal and Urological Systems

Basics of Renal and Urological Systems

• Nephrology: Study of kidneys and kidney-related diseases. "Renal" refers to the kidney.
• Urology: Study of the bladder and bladder-related diseases.
• Humans have two kidneys located in the retroperitoneum.
• Primary kidney functions:
  • Maintain optimal internal environments for tissue and cell metabolism.
  • Manage solute and water balance.
  • Remove metabolic waste.
  • Regulate acids and bases.
  • Produce vitamin D.
  • Produce erythropoietin.
  • Manage blood pressure via the renin-angiotensin-aldosterone system.

Renal and Nephron Anatomy

• Nephron: Functional unit of the kidney; produces urine by filtering plasma through the glomerulus.
• Substances may be reabsorbed or filtered through the renal tubules.
• Urine is collected in the calyces and renal pelvis for transport to the ureter.

Renal and Urinary Tract Anatomy

• Urine travels from the ureter to the bladder.
• Bladder has a nonvoluntary internal urethral sphincter and a voluntary external urethral sphincter.
• Distension of the bladder triggers the micturition reflex and relaxation of the internal urethral sphincter, controlled by sympathetic and parasympathetic nerve fibers.

Urinary Tract Obstruction

• Urinary tract obstruction: Interference with urine flow at any point in the urinary tract.
• Severity depends on:
  • Cause of the lesion.
  • Duration of blockage.
  • Location of the blockage.
  • Degree of completeness.
  • Whether it involves one or both urinary tract systems.
• Classified as upper or lower urinary tract obstruction.

Upper Urinary Tract Obstruction

• Leads to increased hydrostatic pressure and dilation of the ureter, renal pelvis, calyces, renal parenchyma, and glomerulus.
• Reduces glomerular filtration rate (GFR) and causes reflexive dilation (hydroureter, hydronephrosis).
• Chronic dilation can lead to tubulointerstitial fibrosis and apoptosis, affecting kidney function.

Kidney Stones

• Most common cause of upper urinary tract obstruction.
• Also called renal calculi or urolithiasis.
• Masses of crystals, proteins, or mineral salts form in the urinary tract.
• Supersaturation of salts leads to precipitation and crystallization into a stone.
• Inhibitors of stone and crystal formation include pyrophosphate, potassium citrate, and magnesium.
• Risk factors: male gender, inadequate fluid intake, geographic location (high temperature/humidity, dietary patterns).
• Most people with kidney stones develop their first stones before age 50.
• Clinical manifestations: renal pain and signs/symptoms of urinary tract obstruction.
• Treatment:
  • Pain management.
  • Smaller stones may pass without treatment.
  • Larger stones may require lithotripsy (shockwaves or laser to break down stone).
  • Stones causing complications may require surgical removal.
  • Preventative treatment: reduce concentration of stone-forming substances (dietary adjustments and increased fluid intake).

Lower Urinary Tract Obstruction

• Relates to the bladder's ability to empty into the bladder outlet.
• Causes:
  • Neurogenic bladder: Lesions in the brain or spinal cord lead to loss of coordinated neuromuscular contraction.
  • Urethral stricture: Infection, surgery, or injury leads to narrowing of the urethra.
  • Benign prostate hypertrophy: Most common cause in men; enlargement of the prostate obstructs the bladder outlet.

Renal Tumors

• Renal adenomas: Benign solid tumors of the renal cortex that can transform into malignant tumors.
• Renal cell carcinoma: Adenocarcinomas from tubular epithelial cells.
  • Most common malignant renal cancer.
  • Risk factors: male gender, smoking, obesity, hypertension, and renal failure.
  • Clinical manifestations: Hematuria (blood in urine), dull and aching flank pain, palpable flank mass in thinner individuals.
  • Treatment:
    • Localized disease: Surgical removal of the affected kidney (radical nephrectomy) or partial nephron-sparing nephrectomy for smaller tumors.
    • Combination of surgery, chemotherapy, radiation.

Bladder Tumors

• Urothelial carcinoma: Cancer of uroepithelial cells of the inner lining of the ureters, bladder, and urethra.
• Risk factors: smoking, aromatic amines, arsenic in drinking water.
• Clinical manifestations:
  • Gross (visible to the eye) hematuria, which may be episodic and accompanied by other nonspecific urinary tract symptoms such as dysuria (pain while urinating), urgency, incontinence.
• Treatment:
  • Combination surgery, radiation, chemotherapy.

Urinary Tract Infections (UTIs)

• Infections of the urinary tract affecting the urethra, bladder, ureters, or kidneys.
• The most common type of UTI is cystitis, or inflammation/infection of the bladder.
• Typically caused by genitourinary bacterial flora which overgrow or travel backwards into the host’s body (retrograde movement).
• Most common pathogens are E. coli and Staph saprophyticus.
• Risk factors: premature newborns, sexually active and pregnant women, women on certain antibiotics, patients with indwelling urinary catheters, and patients with diabetes mellitus.
• Clinical manifestations of cystitis:
  • Some individuals with mild cystitis may be asymptomatic.
  • Common symptoms include frequency, urgency, dysuria (pain while urinating), hematuria and/or cloudy foul-smelling urine, flank pain.
• Evaluation:
  • Urine culture of specific microorganisms with counts of 10,000/mL or more.
• Treatment:
  • Antimicrobial therapy.

Pyelonephritis

• Infection of the upper urinary tract system (ureters, renal pelvis, kidneys).
• Risk factors: female gender, kidney stones, vesicoureteral reflux, pregnancy, neurogenic bladder, instrumentation, and sexual trauma.
• Clinical manifestations include acute onset of systemic symptoms (fever and chills); may have costovertebral angle tenderness.
  • Typically also have symptoms of UTI.
• May be challenging to differentiate between cystitis and pyelonephritis given similar symptoms; may need diagnostic imaging.
• Treatment is antimicrobial therapy (typically more intense and longer than cystitis).

Acute Glomerulonephritis

• Inflammation of the glomerulus.
• May be caused by immunological responses, ischemic injury, free radicals, drugs, toxins, infections, or as a consequence of chronic diseases such as diabetes or lupus.
  • Immunological responses are most often immune complex mediated (type III hypersensitivity) but may also be type II or IV.
• Leads to decreased glomerular filtration rate (GFR) due to decreased blood flow and scarring.
• Increase in filtration pore size leads to loss of proteins, WBC, and RBCs in the urine.
• Clinical manifestations:
  • Frothy brown-tinged urine (“cola-colored”) from hematuria and proteinuria.
  • Low serum albumin due to loss in urine.
  • Edema caused by decreased intravascular oncotic pressure.
  • Severe or progressive glomerular disease can lead to eventual oliguria (urine output <30 mL/hour).
• Treatment:
  • Supportive care.
  • Find and treat underlying cause.

Chronic Glomerulonephritis

• If left untreated, acute glomerulonephritis can become chronic and eventually lead to chronic kidney disease.
• Most commonly chronic glomerulonephritis is due to secondary causes such as diabetes or lupus.
• Injury to the glomeruli can also lead to nephritic and nephrotic syndromes.

Nephritic and Nephrotic Syndrome

Nephrotic Syndrome

• Glomeruli injury to the basement membrane leads to escape of proteins.
• Urinary protein excretion of 3.5 g or more.
• Hypoalbuminemia, edema, and hyperlipidemia.

Nephritic Syndrome

• Immune complexes and inflammation at the glomeruli leads to increased permeability of glomerular filtration membrane.
• Mild proteinuria (<3.5 g) with hematuria.
• Urinary RBC and WBC casts with varying amounts of proteinuria.
• Patients tend to develop hypertension.

Renal Failure

• Renal failure develops once kidney function becomes impaired.
• Measured by serum creatinine levels, glomerular filtration rate (GFR), and albuminuria.
• Categorized as:
  • Acute (sudden onset; may be temporary or irreversible depending on underlying cause).
  • Chronic (progressive renal failure typically caused systemic disease process).
• Other common terms:
  • Renal insufficiency: renal function reduced by 25%.
  • Renal failure: renal function reduced significantly.
  • End stage renal disease: less than 10% of renal function remains.

Acute Kidney Injury (AKI)

• Sudden decline in kidney function.
  • Clinically measured by decreased GFR, increased serum creatinine, increased blood urea nitrogen (BUN), and reduced urine output.
• Causes:
  • Pre-renal: Inadequate renal perfusion leads to eventual decrease in glomerular filtration pressure.
    • Examples: hypotension of any cause, hypovolemia from acute blood loss/hemorrhage, renal vasoconstriction caused by NSAIDs (ibuprofen), etc.
  • Intrarenal: Direct injury of renal parenchyma or interstitial cells.
    • Examples: acute tubular necrosis, exposure to nephrotoxic contrast dye, acute glomerulonephritis, graft rejection.
  • Post renal: Urinary tract obstruction leads to increased intratubular pressure and decreased GFR.
    • Tumors, kidney stones, neurogenic bladder, etc.
• Clinical manifestations:
  • Fatigue, nausea, vomiting.
  • Oliguria: Reduced urine output of less than 30 mL/hour.
  • Anuria: Severely reduced urine output of less than 10 mL/hr or complete absence of urine production.
  • Electrolyte disturbances: Hyperkalemia and hyperphosphatemia.
  • Metabolic acidosis: Secondary to hyperkalemia.
  • Decreased GFR, elevated BUN and creatinine.
• Prevention:
  • Maintenance of fluid volume before and after surgery/diagnostic procedures when nephrotoxic drugs or contrast agents are used.
• Treatment:
  • Supportive care.
    • Correct fluid and electrolyte disturbances (especially hyperkalemia).
    • Manage normal blood pressure levels.
    • Prevent and treat infections.
    • Maintain adequate nutrition.
    • Avoid nephrotoxic medications.
  • May need temporary dialysis if severe.
  • If reversible, recovery may take up to a year.

Chronic Kidney Disease (CKD)

• Progressive loss of renal function; typically caused by underlying systemic diseases such as uncontrolled hypertension, diabetes, systemic lupus erythematosus, or intrinsic kidney disease.
• Similar to AKI, can be clinically measured by decreased GFR, increased serum creatinine, increased blood urea nitrogen (BUN), degree of albuminuria, and reduced urine output.
• Factors that contribute to advancing disease progression include proteinuria and angiotensin II.
  • Proteinuria contributes to tubulointerstitial injury by promoting inflammation and progressive fibrosis.
  • Angiotensin II promotes glomeruli hypertension which may progress to tubulointerstitial fibrosis and scarring.
• Clinical manifestations are similar to AKI however they do not typically appear until after 25% of renal function is lost.
• Can develop life-threatening hyperuremic syndrome.
  • Toxic build up of end-products of metabolism leading to hypertension, anorexia, nausea/vomiting, diarrhea, constipation, malnutrition, weight loss, seizures, cardiovascular disease, etc.
• Other considerations in CKD:
  • Edema and fluid overload are common.
    • Patients will need careful balance of salt and water intake in diet.
    • Too much fluid may result in pulmonary edema and dyspnea.
    • May gain weight due to fluid build up.
  • Decreased urinary excretion of potassium and phosphate lead to electrolyte disturbances.
    • High potassium can lead to life-threatening cardiac irregularities.
    • High potassium also results in metabolic acidosis.
    • High phosphate leads to low levels of calcium.
  • Patients develop altered protein, carbohydrate and fat metabolism.
    • Nausea and vomiting can lead to malnutrition and weight loss.
    • Also associated with glucose intolerance and dyslipidemia.
  • Cardiovascular abnormalities are more common in patients with CKD.
    • Hypertension, glucose intolerance, inflammation, potassium abnormalities can all lead to increased risk of cardiovascular disease.
  • Hematological considerations.
    • Kidneys are responsible for producing erythropoietin to simulate new production of RBCs; failing kidneys means less or no erythropoietin and development of anemia.
    • Loss of protein leads to loss of plasma proteins including coagulation cascade; patients will be more prone to bleeding.
    • Loss of plasma proteins including complement cascade; patients will be more likely to develop infections.
• Bottom line: Our kidneys are vital for the proper functioning of every single systems within our body. Lack of kidney activity will eventually progress to death.

Dialysis

• Two ways to perform dialysis in patients with end stage renal disease: Hemodialysis and Peritoneal dialysis.

Kidney Transplantation

• Some patients with end-stage renal disease may be candidates for a renal transplant.
• In renal transplants, the old kidneys are typically left in place (except in cases of renal carcinoma).
• The newly transplanted kidney may come from either a living or deceased donor and is placed in the lower abdomen near the pelvis.
• It may take several days to weeks for the newly transplanted kidney to start working (especially if it is from a deceased donor).
• There are some instances in which the newly transplanted kidney is rejected (allograft rejection).
  • Patient who receive solid-organ transplants will need to be on life-long immunosuppressant therapy to prevent this from occurring.
  • Some transplants will fail despite compliance to medications.

Renal Failure Clinical Pearls

• How do you know when to start a patient on dialysis or other renal replacement therapy in AKI?
  • AEIOU (acidosis, electrolyte abnormalities that are life-threatening, intoxication, overload, uremia).
• Patients who have reduced kidney function will need to have their medications reviewed periodically to ensure they are given the correct dosages.
  • May need reduced dosages of certain medications or certain medications may be contraindicated.

Pediatric Nephrological Diseases

Congenital Abnormalities

• Anatomical renal abnormalities.
  • Ectopic kidney: kidneys fail to ascend into abdomen from the pelvis.
  • Horseshoe kidney: kidneys fuse in the middle of the abdomen as they ascend.
  • Renal agenesis: absence of one or both kidneys; remaining kidney is typically normal but becomes hypertrophic and prone to developing CKD due to increased stress on organ.
• Anatomical urinary tract abnormalities.
  • Vesicoureteral reflux: malfunctioning valve allows backwards flow of urine; common presenting symptoms are frequent UTIs.
  • Congenital bladder outlet obstructions.

Hemolytic Uremic Syndrome (HUS)

• Acute disorder characterized by hemolytic anemia, thrombocytopenia, and renal impairment.
• Most common community-acquired cause of acute renal failure in children.
• Associated with bacterial and viral endotoxin agents (especially E. coli O157:H7).
  • Bacterial toxin causes lysis of RBCs and activation of coagulation cascade and platelets.
  • Toxin also travels to the kidneys, where it causes lysis of endothelial basement membrane cells of the glomeruli.
  • Arterioles of the glomerulus become swollen and occluded with fibrin clots.
  • This leads to further destruction of RBCs as they pass through the swollen glomeruli blood vessels.
• Clinical manifestations:
  • Classic presentation is prodromal gastrointestinal illness with diarrhea followed by sudden onset of severe HUS symptoms 1-2 weeks later.
    • HUS symptoms include anemia due to destruction of RBC.
    • Stimulation of platelets leads to microthrombi while overuse and depletion of coagulation plasma proteins leads to easy bruising, purpura, and bloody diarrhea.
    • Acute renal failure symptoms such as volume overload, oliguria, hypertension, metabolic acidosis, hyperkalemia, etc.
    • Classic triad – anemia, thrombocytopenia, and AKI.
• Emergency condition but most children will recover with proper treatment.
  • Supportive care (nutrition, hydration, dialysis, transfusions as needed, etc).

Wilms Tumor

• Malignant embryonal tumor of the kidney also known as nephroblastoma.
• Most common solid tumor of childhood.
  • Peak incidence is around 2-3 years of age.
• Can develop sporadically or from genetic inheritance.
• “Two-hit” hypothesis.
  • Wilms tumor-suppressor genes WT1 and WT 2 are located on chromosome 11.
  • Children who inherit a mutation in one allele of a tumor-suppression gene require just one more somatic mutation for a tumor to form.
• Clinical manifestations:
  • Most common presentation is an enlarging asymptomatic upper abdominal mass in a healthy, thriving child.
  • As mass grows, child may experience vague abdominal pain, hematuria, fever, and hypertension.
• Treatment:
  • Cancer staging for prognosis and treatment.
  • Surgery, chemotherapy, radiation.