Acute Renal Failure: Causes

Pathogenesis (development of disease)

In acute renal failure (ANV), there is a sudden loss of excretory function of the kidneys, which is usually initially accompanied by oliguria (< 500 ml urine/day). Pathophysiologically, acute renal failure can be divided into three forms:

  • Prerenal renal failure (70%): caused by a sudden or prolonged reduction in renal perfusion (kidney blood flow):
    • Reduction in effective circulating blood volume: e.g., because of volume deficiency, peripheral vasodilation (vasodilatation), or pumping failure of the heart
    • Mechanical restriction of renal perfusion: for example, because of aortic valve stenosis, renal artery stenosis (see below).
  • Renal kidney failure (20%): due to classic renal causes (glomerular and postglomerular diseases; cardiorenal syndrome; hepatorenal syndrome; pregnancy-associated damage); see also “Risk factors for the development of acute kidney injury”
  • Postrenal renal failure (10%): due to obstruction of urinary outflow from the kidney unilaterally or bilaterally.

Risk factors for developing acute kidney injury:

  • Female gender
  • Age – older age
  • Diabetes mellitus requiring insulin
  • Heart failure (cardiac insufficiency)
  • Left ventricular ejection fraction (ejection fraction of the left ventricle) < 35%.
  • Chronic obstructive pulmonary disease (COPD)
  • Infections
  • Sepsis (blood poisoning)
  • Fluid overload
  • Nephrotoxic drugs (drugs that damage the kidneys; see below).
  • Surgeries: Cardiac surgery (inbes. use of the heart–lung machine; long aortic clamping times); use of the intra-aortic balloon pump; emergency interventions or reinterventions.

Etiology (causes) of prerenal acute renal failure

Prerenally triggered forms of acute renal failure are due to a reduction in effective blood volume (= absolute volume deficiency). This results in secondary ischemic (decreased blood flow) damage to nephrons (consists of the renal corpuscle (Malpighi corpuscle) and the attached renal tubule – tubule). Disease-related causes

Blood, hematopoietic organs – immune system (D50-D90).

  • Hemolysis – dissolution of erythrocytes (red blood cells).
  • Hemolytic uremic syndrome (HUS) – triad of microangiopathic hemolytic anemia (MAHA; form of anemia in which erythrocytes (red blood cells) are destroyed), thrombocytopenia (abnormal reduction in platelets/platelets), and acute kidney injury (AKI); Mostly occurring in children in the context of infections; most common cause of acute renal failure requiring dialysis in childhood.
  • Hemorrhage (bleeding), unspecified.
  • Hypoproteinemia – decrease in the protein content of the blood.

Endocrine, nutritional and metabolic diseases (E00-E90).

  • Hypercalcemia (excess calcium).
  • Hyperoxaluria (synonym: oxaluria, oxalosis) – increase and increased excretion of oxalic acid in urine.
  • Hypovolemia (volume deficiency)
  • Adrenocortical insufficiency
  • Nephrogenic diabetes insipidus
  • Tumor lysis syndrome (life-threatening metabolic derailment that can occur when a large number of tumor cells are suddenly destroyed), incl.: Tumor lysis (after cytostatic therapy).

Cardiovascular System (I00-I99).

  • Aortic valve stenosis (narrowing of the aortic valve).
  • Aortic dissection (synonym: aneurysm dissecans aortae) – acute splitting (dissection) of the wall layers of the aorta (main artery), with a tear of the inner layer of the vessel wall (intima) and hemorrhage between the intima and the muscular layer of the vessel wall (outer media), in the sense of an aneurysm dissecans (pathological expansion of the artery).
  • Cholesterol embolism syndrome – caused by the occlusion of small arteries by wash-in (embolism) of cholesterol crystals from broken (ulcerated) arteriosclerotic plaques.
  • Heart failure (cardiac insufficiency)
  • Malignant hypertension – severe progression of hypertension with a systolic blood pressure of more than 180 mmHg and / or a diastolic blood pressure of more than 110 mmHg, which is usually accompanied by significant symptoms
  • Myocardial infarction (heart attack) with heart failure (cardiac insufficiency).
  • Myocarditis (inflammation of the heart muscle) with heart failure (cardiac insufficiency).
  • Renal artery stenosis (narrowing of the renal artery).
  • Thromboembolism – occlusion of a blood vessel by a detached blood clot.
  • Thrombotic microangiopathy (TMA) due to tumor disease – heterogeneous group of diseases that, in conjunction with endothelial damage, lead to thrombosis of small arterial as well as venous vessels; characterized by mechanical hemolysis (dissolution of red blood cells), low-grade to severe thrombocytopenia (lack of platelets) and acute renal failure.

Infectious and parasitic diseases (A00-B99).

  • Sepsis (blood poisoning)

Liver, gallbladder, and bile ducts-pancreas (pancreas) (K70-K77; K80-K87).

  • Hepatorenal syndrome (HRS) – functional, in principle fully reversible decrease in glomerular filtration rate (total volume of primary urine an, which is filtered by all glomeruli (renal corpuscles) of both kidneys together, in a defined unit of time, is filtered) resulting in oliguric renal failure (in oliguric renal failure, the kidneys give < 500 ml of urine production / day) in patients with liver cirrhosis (irreversible damage to the liver and a pronounced remodeling of liver tissue) or fulminant hepatitis (liver inflammation) in the absence of evidence of other causes of renal failure (slowly progressive reduction in renal function).
  • Pancreatitis (inflammation of the pancreas).

Mouth, esophagus (esophagus), stomach, and intestines (K00-K67; K90-K93).

  • Diarrhea (diarrhea)
  • Vomiting
  • Peritonitis (inflammation of the peritoneum)

Musculoskeletal system and connective tissue (M00-M99)

  • Rhabdomyolysis – dissolution of striated muscle fibers as a complication of various diseases/conditions (e.g., statins).

Neoplasms – tumor diseases (C00-D48).

  • Plasmocytoma (multiple myeloma) due to “overflow proteinuria,” i.e., due to exceeding the tubular reabsorption capacity because of an oversupply of proteins.

Causes (external) of morbidity and mortality (V01-Y84).

Injuries, poisonings, and other consequences of external causes (S00-T98).

  • Anaphylaxis – most severe allergic reaction.
  • Bleeding
  • Heat stroke
  • Hypothermia (hypothermia)
  • Perforation of hollow organs
  • Rhabdomyolysis – dissolution of striated muscle fibers as a complication of various diseases/conditions.
  • Burns

Laboratory diagnoses – laboratory parameters that are considered independent risk factors.

Other causes

  • Volume loss due to surgical drainage
  • Condition after major surgical procedures in the thorax (chest) or abdomen (stomach) region.

Etiology (causes) of renal (intrarenal) acute renal failure

Intrarenally triggered forms of acute renal failure rely on primary damage to nephrons from. This often results in extensive tubular necrosis (death of renal tubules), leading to deposition of cellular debris in the tubular lumen. Disease-related causes

Blood, hematopoietic organs – immune system (D50-D90).

  • Hemolysis – dissolution of erythrocytes (red blood cells).
  • Sarcoidosis – granulomatous inflammation; multi-system inflammatory disease.

Endocrine, nutritional and metabolic diseases (E00-E90).

  • Adrenocortical insufficiency
  • Nephrogenic diabetes insipidus

Infectious and parasitic diseases (A00-B99).

Musculoskeletal system and connective tissue (M00-M99).

  • Rhabdomyolysis – pathological dissolution of muscle fibers as a complication of various diseases/conditions.

Neoplasms – tumor diseases (C00-D48).

  • Cast nephropathy in the context of a plasmacytoma (multiple myeloma) – malignant tumor disease from the group of non-Hodgkin’s lymphomas. Its origin is in the lymphoid tissue, as with all lymphomas.
  • Malignancy (tumor disease) with renal infiltration.

Psyche – nervous system (F00-F99; G00-G99)

Genitourinary system (kidneys, urinary tract – reproductive organs) (N00-N99).

  • Glomerular diseases
  • Postglomerular diseases
    • Acute interstitial nephritis (kidney inflammation) (symptoms: immunologic hypersensitivity reaction; triad of fever, exanthema/rash, and eosinophilia/increase in normal blood eosinophil granulocyte count show in only 10-20% of patients; causes: Antibiotics (cephalosporins, penicillins), diuretics (furosemide, thiazides), NSAIDs; allopurinol, cotrimoxazole, rifampicin, omeprazole).
    • Acute tubular necrosis (ATN) – kidney disease caused by short-term damage to the cells of the tubular system.
    • KM-induced nephropathy (English contrast-induced nephropathy, CIN) – one of the main causes of the development of acute renal failure (ANV).
    • Myeloma kidney (synonym: cast nephropathy; cast: English for cylinder) – classic form of kidney damage in multiple myeloma.
    • Renal artery stenosis – unilateral or bilateral narrowing of the artery supplying the kidneys (renal artery).
    • Obstructive uropathy (synonyms: urinary retention; urinary stasis; urinary retention) -congestion of urine of varying severity due to an obstruction of outflow in the urinary tract.

Laboratory diagnoses – laboratory parameters that are considered independent risk factors.

Drugs (nephrotoxic: nephrotoxic (damaging to the kidney) drugs/nephrotoxic drugs).

  • ACE inhibitors and AT1- receptor antagonists (acute: decrease in glomerular filtration rate (GFR) associated with creatinine increase: ACE inhibitors as well as AT1 receptor antagonists abolish vasoconstriction (vasoconstriction) in the vas efferens, and a decrease in GFR and increase in serum creatinine result. Up to 0.1 to 0.3 mg/dl, this is usually tolerable.However, in the presence of hemodynamically relevant renal artery stenosis (not uncommon in patients with atherosclerosis/arteriosclerosis), GFR becomes markedly angiotensin II-dependent, and administration of an ACE inhibitor or AT1 receptor antagonist may result in acute renal failure)!
  • Angiotensin receptor neprilysin antagonists (ARNI) – dual drug combination: sacubitril/valsartan.
  • Antiphlogistic and antipyretic analgesics (non-steroidal anti-inflammatory drugs (NSAID), nonsteroidal anti-inflammatory drugs) or non-steroidal anti-inflammatory drugs (NSAIDs* ) Caution: the combination of a diuretic, an RAS blocker, and an NSAID is associated with a significant risk of acute kidney injury:
    • Acetylsalicylic acid (ASA).
    • Diclofenac
    • Ibuprofen/naproxen
    • Indometacin
    • Metamizole (novaminsulfone) is a pyrazolone derivative and analgesic from the group of non-acidic non-opioid analgesics (highest analgesic and antipyretic activity. Side effects: Circulatory fluctuations, hypersensitivity reactions, and very rarely agranulocytosis.
    • Paracetamol / acetaminophen
    • Phenacetin (phenacetin nephritis)
    • Selective COX-2 inhibitors such as rofecoxib, celecoxib (side effects: decreased sodium and water excretion, blood pressure increase and peripheral edema. This is usually accompanied by hyperkalemia!).
  • Selective COX-2 inhibitors such as rofecoxib, celecoxib (side effects: decreased sodium and water excretion, blood pressure increase and peripheral edema. This is usually accompanied by hyperkalemia!).
  • Antibiotics
  • Antidiabetics
  • Antifungals
    • Polyenes (amphotericin B, natamycin)
  • Colchicine
  • Diuretics
  • D-Penicillamine
  • Gold – sodium aurothiomalate, auranofin
  • Immunosuppressants (ciclosporin (cyclosporin A)) – esp. ciprofloxacin plus ciclosporin A.
  • Interferon
  • Colloidal solution with hydroxyl starch
  • Contrast media – Of particular importance here are magnetic resonance imaging (MRI) contrast media containing gadolinium, which can lead to nephrogenic systemic fibrosis (NSF). Particularly affected by NSF are patients with a glomerular filtration rate (GFR) of less than 30 ml/min. [CKD stage 4]; iodine-containing radiographic contrast agents; [require prophylactic irrigation in renal insufficiency]EMA (European Medicines Agency): categorization of GBCAs (gadolinium-based contrast agents) in terms of NSF (nephrogenic systemic fibrosis) risk, based on thermodynamic and kinetic properties:
    • High risk: gadoversetamide, gadodiamide (linear/non-ionic chelates) gadopentetate dimeglum (linear/ionic chelate).
    • Medium risk: gadofosveset, gadoxetic acid disodium, gadobenate dimeglumine (linear/ionic chelates).
    • Low risk: gadoterate meglumine, gadoteridol, gadobutrol (macrocyclic chelates).

    Note: Neither sodium bicarbonate nor acetylcysteine (ACC) provides protection against contrast-induced acute kidney injury during angiography.

  • Lithium
  • Oncological therapy (oncologics).
  • Proton pump inhibitors (proton pump inhibitors, PPI; acid blockers).
    • “Atherosclerosis Risk in Communities” (ARIC): 10-year PPI use: rate of chronic renal failure in patients on PPI 11.8%, without 8.5%; rate of renal damage: 64%; two pills a day resulted in significantly more frequent damage: 62%
    • Geisinger Health System: observation period 6.2 years; rate of chronic renal failure disease: 17%; rate of renal damage: 31%; two pills a day resulted in significantly more frequent damage: 28%
  • Rast blockers: the combination of a diuretic, an RAS blocker, and an NSAID is associated with a significant risk of acute kidney injury.
  • X-ray contrast agent
  • Statins (rhabdomyolysis)
  • Tacrolism (macrolide derived from the gram-positive bacterium Streptomyces tsukubaensis. Tacrolimus is used as a drug in the group of immunomodulators or calcineurin inhibitors).
  • Antivirals

Environmental pollution – intoxications (poisonings).

  • Aliphatic hydrocarbons (2,2,4-trimethylpentane, decalin, unleaded gasoline, mitomycin C).
  • Ethanol (ethanol; alcohol)
  • Ethylene glycol (ethylene glycol)
  • Halogenated hydrocarbons (HFC; trichloroethene, tetrachloroethene, hexachlorobutadiene, chloroform).
  • Herbicides (paraquat, diquat, chlorinated phenoxyacetic acids).
  • Cocaine
  • Melamine
  • Metals (cadmium, chromium, lead, lithium, nickel, mercury, uranium).
  • Mycotoxins (ochratoxin A, citrinin, aflatoxin B1).
  • Salicylates

Etiology (causes) of postrenal acute renal failure

Postrenally triggered forms of acute renal failure are due to obstruction (occlusion) in the urinary tract. This results in anuria (less than 100 ml of urine in 24 hours) and an increase in pressure above the outflow obstruction. As a result, blood flow to the kidney is throttled. Disease-related causes

Congenital malformations, deformities, and chromosomal abnormalities (Q00-Q99).

  • Malformations of the genitourinary system

Neoplasms – tumor diseases (C00-D48)

  • Tumors of the reproductive organs, unspecified.
  • Tumors of the retroperitoneal space (space between the peritoneum and the posterior abdominal wall), unspecified
  • Tumors of the genitourinary tract, unspecified.

Genitourinary system (kidneys, urinary tract – reproductive organs) (N00-N99).

  • Benign prostatic hyperplasia – benign enlargement of the prostate gland.
  • Ureteral stenosis (ureteral stricture)
  • Urethrastenosis (urethral narrowing)
  • Urolithiasis (urinary stone disease)

Medication

Other causes

  • Obstructed/dislocated urinary bladder indwelling catheters.