Renal system

Question 1

Acute kidney injury

Answer 1

Acute kidney injury (AKI) is a sudden loss of renal function with a consecutive rise in creatinine and blood urea nitrogen (BUN). It is most frequently caused by decreased renal perfusion (prerenal) but may also be due to direct damage to the kidneys (intrarenal or intrinsic) or inadequate urine drainage (postrenal). In AKI, acid-base homeostasis, as well as the fluid and electrolyte balance, is disturbed, and the excretion of substances, including drugs, within the urine is impaired. The main symptom of AKI is oliguria or anuria; in some cases, polyuria may occur as a result of disturbed tubular reabsorption. Diagnosis of AKI requires an increase in serum creatinine concentration and/or decrease in urine output. Specific investigations are guided by the suspected cause. Rapid evaluation, diagnosis, and treatment are necessary to prevent irreversible loss of renal function.

Aetiology:
Prerenal acute kidney injury (∼ 60% of cases)
Prerenal causes include any condition leading to decreased renal perfusion.
Hypovolemia
Volume depletion: e.g., hemorrhage, vomiting, diarrhea, sweating, burns, diuretics, poor oral intake, acute pancreatitis
Decreased circulating volume: e.g., hepatorenal syndrome, cirrhosis, liver failure, nephrotic syndrome, congestive heart failure
Hypotension: e.g., sepsis, dehydration, cardiogenic shock (decreased cardiac output), anaphylactic shock
Renal artery stenosis
Drugs affecting glomerular perfusion: e.g., cyclosporine, tacrolimus, NSAIDs , ACE inhibitors
Avoid coadministering ACE inhibitors and NSAIDs in patients with reduced renal perfusion (e.g., congestive heart failure, renal artery stenosis) because doing so can significantly decrease the glomerular filtration rate (GFR)!
Intrinsic acute kidney injury (∼ 35% of cases)
Intrinsic causes include any disease that leads to severe direct kidney damage.
Acute tubular necrosis (causes ∼ 85% of intrinsic AKIs): most commonly caused by sepsis, infection, ischemia, and/or nephrotoxins
Glomerulonephritis (e.g., rapidly progressive glomerulonephritis)
Vascular
Hemolytic uremic syndrome (HUS)
Thrombotic thrombocytopenic purpura (TTP)
Malignant hypertension
Vasculitis
Acute tubulointerstitial nephritis
Drug-induced
Infectious
Immunological
Prolonged prerenal failure leads to intrinsic failure because decreased renal perfusion causes tubular necrosis!
Postrenal acute kidney injury (∼ 5% of cases)
Postrenal causes include any condition that results in bilateral obstruction of urinary flow from the renal pelvis to the urethra.
Congenital malformations (e.g. posterior urethral valves)
Acquired obstructions
Benign prostatic hyperplasia (BPH)
Iatrogenic/catheter-associated injuries
Tumors
Stones
Bleeding with blood clot formation
Neurogenic bladder (e.g., multiple sclerosis, spinal cord lesions, or peripheral neuropathy)
As long as the contralateral kidney remains intact, patients with unilateral ureteral obstruction typically maintain normal serum creatinine levels.

Pathophysiology
Prerenal
Decreased blood supply to kidneys (due to hypovolemia, hypotension, or renal vasoconstriction) → failure of renal vascular autoregulation to maintain renal perfusion → decreased GFR → activation of renin-angiotensin system → increased aldosterone release → increased reabsorption of Na+, H2O → increased urine osmolality → secretion of antidiuretic hormone → increased reabsorption of H2O and urea
Creatinine is still secreted in the proximal tubules, so the blood BUN:creatinine ratio increases.
Mechanism of action: renin-angiotensin-aldosterone system (RAAS) inhibitors
Intrinsic
Damage to a vascular or tubular component of the nephron → necrosis or apoptosis of tubular cells → decreased reabsorption capacity of electrolytes (e.g., Na+), water, and/or urea (depending on the location of injury along the tubular system) → increased Na+ and H2O in the urine → decreased urine osmolality
Postrenal
Bilateral urinary outflow obstruction (e.g., stones, BPH, neoplasia, congenital anomalies) → increased retrograde hydrostatic pressure within renal tubules → decreased GFR and compression of the renal vasculature → acidosis, fluid overload, and increased BUN, Na+, and K+.
A normal GFR can be maintained as long as one kidney functions normally.

Clinical features 
May be asymptomatic.
Oliguria or anuria
Signs of volume depletion (in prerenal AKI caused by volume loss)
Orthostatic or frank hypotension and tachycardia
Reduced skin turgor
Signs of fluid overload (from Na+ and H2O retention)
Peripheral and pulmonary edema
Hypertension
Heart failure
Shortness of breath
Signs of uremia
Anorexia, nausea
Encephalopathy, asterixis
Pericarditis
Platelet dysfunction
Signs of renal obstruction (in postrenal AKI)
Distended bladder
Incomplete voiding
Pain over the bladder or flanks
Fatigue, confusion, and lethargy
In severe cases: seizures or coma
Affected individuals have a higher risk of secondary infection throughout all phases  (most common reason for fatalities).

Investigations
The diagnosis of AKI requires an acute increase in serum creatinine and/or decrease in urine output (see the criteria for different stages in the table below); therefore, renal function tests should be done in every patient with suspected AKI
Additional laboratory investigations and imaging should be guided by the suspected cause.
Prerenal
Blood test findings
Elevated serum creatinine concentration
Serum BUN:creatinine ratio > 20:1
Urine test findings
Normal urinalysis
Low urine sodium concentration (< 20 mEq/L)
Low fractional excretion of sodium (FeNa < 1%)
The fractional excretion of sodium reveals how much filtered sodium is excreted in the urine.
FENa = (VUNa)/(GFRPNa), using plasma and urine sodium concentrations (PNa and UNa), urine flow rate (V), and GFR or
FENa = (SCrUNa)/(SNaUCr), using serum sodium (SNa), urine sodium (UNa), serum creatinine (SCr), and urine creatinine (UCr).
High urine osmolality (> 500 mosm/kg) and specific gravity (> 1.010)
Hyaline casts due to hypovolemia resulting in concentrated urine
Intrinsic
Blood test findings
Elevated serum creatinine concentration and rapidly rising serum creatinine level
BUN:creatinine ratio < 15:1.
Markedly elevated serum CPK level (10,000–100,000) in rhabdomyolysis
Hyperkalemia, metabolic acidosis, hyperphosphatemia, hypocalcemia, hyperuricemia, and/or dyslipidemia (especially hypertriglyceridemia) may be seen.
Low Hb (anemia) due to decreased EPO
Urine test findings
Renal tubular epithelial cells or granular, muddy brown, or pigmented casts
Urine dipstick is positive for blood but negative for RBCs in rhabdomyolysis
Biopsy: in suspected rapidly progressive glomerulonephritis
Postrenal
Blood test findings
Elevated serum creatinine concentration in bilateral obstruction
BUN:creatinine ratio varies.
Urine test findings
Normal urinalysis (neurogenic bladder)
Hematuria (stones, bladder cancer, clots)
Imaging: high post-void residual volume and bilateral hydronephrosis on renal ultrasound or noncontrast CT scan.
Consequences of acute and chronic renal failure (MAD HUNGER): Metabolic Acidosis, Dyslipidemia, High potassium, Uremia, Na+/H2O retention, Growth retardation, Erythropoietin failure (anemia), Renal osteodystrophy.

Treatment
General measures
Treat the underlying cause.
Patient should discontinue nephrotoxic substance use.
Adjust dosages of medications cleared by the kidney (e.g., amiodarone, digoxin, cyclosporin, tacrolimus, antibiotics, chemotherapeutic agents).
Monitor and manage changes in pH, water, and electrolyte balance.
Assess uremic signs and symptoms (e.g., anorexia, nausea, vomiting, metallic taste, altered mental status) daily
Perform dialysis if necessary. (See indications for acute dialysis.)
Prerenal
Replete volume with normal saline in patients with hypovolemia
Administer diuretics in patients with hypervolemia who are hemodynamically stable and not anuric
Intrinsic
Replete volume with normal saline in suspected ATN or contrast-induced renal dysfunction
Consider corticosteroid or immunosuppressive therapy in RPGN or interstitial nephritis.
Treat infection.
Postrenal: Remove outflow obstructions with Foley catheter insertion, an indwelling bladder catheter, nephrostomy, or stenting.
The longer the underlying cause, the greater the chance that AKI progresses to chronic renal failure. Treat early!

Question 2

Chronic kidney diseasse

Dr Deac Pimp

Answer 2

Chronic kidney disease (CKD) is defined as an abnormality of the kidney structure or function for ≥ 3 months. The most common causes of CKD in the United States are diabetes mellitus, hypertension, and glomerulonephritis. Since the kidneys have exceptional compensatory mechanisms, most patients remain asymptomatic and are unaware of their condition until their kidney function is significantly impaired. Patients typically present with symptoms of fluid overload (e.g., peripheral edema) and uremia. Laboratory evaluation shows hyperkalemia, hyperphosphatemia, and hypocalcemia, as well as metabolic acidosis. Management focuses mainly on treating the underlying disease and preventing possible complications, e.g., treating hypertension, avoiding nephrotoxic substances, and maintaining adequate hydration. If chronic kidney disease progresses to end-stage renal disease (ESRD), renal replacement therapy (dialysis) or a kidney transplant is necessary.

Definition:
Chronic kidney disease is defined as an abnormality of the kidney structure or function for ≥ 3 months.
Associated with an irreversible reduction of the excretory (glomerular, tubular) and the endocrine functions of the kidney

Epidemiology
About 10% of adults in the US suffer from chronic kidney disease.
African Americans are at increased risk of developing chronic kidney disease.

Aetiology
-Diabetic nephropathy: most common cause, accounts for 44% of cases in the US
-Hypertensive nephropathy
-glomerulonephritis
-polycystic kidney disease/hereditary
-Urological disease
Other causes: amyloidosis, toxins, chronic inflammation

Clinical features:
Patients are often asymptomatic until later stages.
Hypertension
Peripheral edema
Pulmonary edema (usually interstitial pulmonary edema)
Clinical features of uremia
Fatigue, weakness, loss of appetite, headaches
Uremic fetor
Pigmented spots
Pruritus
Anemia
Uremic pericarditis
Friction rub on auscultation
Diagnostics: Uremic pericarditis does not show typical ECG changes such as diffuse ST-segment elevation.
Pleuritis
Asterixis
Encephalopathy: seizures, somnolence, coma
Peripheral neuropathy: paresthesias
Gastrointestinal symptoms: nausea, vomiting
↑ Risk of infection: leukocyte dysfunction
↑ Bleeding tendency secondary to platelet dysfunction
Chronic kidney disease-mineral and bone disorder (CKD-MBD): abnormalities of mineral or bone metabolism in the setting of chronic renal disease
Etiology: mostly due to secondary hyperparathyroidism → high-turnover renal osteodystrophy or osteitis fibrosa cystica
Clinical features: weakness, fractures, bone pain, avascular necrosis
Patients develop secondary hyperparathyroidism and subsequent renal osteodystrophy due to hyperphosphatemia, hypocalcemia, and the insufficient production of vitamin D!

Different stages/classification on word.

Investigation:
Blood
↑ Creatinine and BUN
Electrolytes: hyperkalemia, hyperphosphatemia, hypocalcemia
Monitor blood pH for metabolic acidosis
↓ Calcitriol levels
↑ Parathyroid hormone (PTH)
Coagulation testing: ↔︎ PT, PTT, platelet count, ↑ bleeding time caused by uremic coagulopathy
Anemia of chronic kidney disease: ↓ hemoglobin, ↔︎ MCV
Pathophysiology: ↓ erythropoietin → decreased stimulation of RBC production → normocytic, normochromic anemia
Urinalysis: possibly abnormal urine sediment (see nephritic sediment, nephrotic sediment)
Ultrasound: shrunken kidneys and fibrotic parenchyma
Renal biopsy: sometimes indicated to determine the underlying cause
In chronic renal disease, close surveillance of serum potassium values as well as calcium and phosphate values is essential!

Treatment
Diet
Salt restriction in patients with edema or hypertension
See treatment of hyperkalemia.
See treatment of acid-base disorders.
Nephrotoxic substances avoidance
NSAIDs
Nicotine
Sulfonamide antibiotics, aminoglycosides, vancomycin
Acyclovir
Cisplatin
Others (e.g., lead, amphetamines, amphotericin B, radiographic contrast material)
Strict blood pressure control
Well-controlled blood pressure is essential to prevent disease progression.
See treatment of hypertension.
Vaccinations
All patients with CKD
Pneumococcal vaccine every 5 years
Influenza vaccine annually
Susceptible patients: hepatitis B vaccine (see high-risk groups for HBV infection)
Special patient groups
End-stage renal disease
Dialysis until a renal transplant is available
Anemia of chronic kidney disease
Administer synthetic EPO, possibly in conjunction with iron replacement depending on serum ferritin and transferrin values.
Adverse effects: increased risk of thrombosis, increase in blood pressure
RBC transfusion may be needed in cases of EPO resistance
Metabolic diseases
Hyperlipidemia: statins
Diabetes mellitus: Insulin dose may have to be decreased.
Restrict protein intake to 0.8–1.0 g/kg/day
Actively bleeding or about to undergo a surgical procedure
Desmopressin (DDAVP): first-line therapy
Cryoprecipitate: life-threatening bleeding resistant to treatment with desmopressin
Conjugated estrogens: for chronic control of bleeding
Correction of anemia
Dialysis