Disorders of the kidney and urinary tract Flashcards
a) Define AKI and it’s diagnostic features
b) What are the 5 most common causes of AKI and what 4 clinical settings often preceed it?
c) What are the 3 broad categories that cause AKI?
a) AKI is defined by the impairment of kidney filtration and excretory function over days to weeks. It represents a heterogenous group of conditions that share common diagnostic features e.g. Increase in serum creatinine (SCr), reduction in urine volume and reduction in eGFR.
b) Common causes include volume depletion, heart failure, adverse effects of medications, obstruction of the urinary tract, or malignancy. The most common clinical settings for AKI are sepsis, major surgical procedures, critical illness involving heart or liver failure, and nephrotoxic medication administration.
c) Prerenal Azotemia (azo=nitrogen; emia=blood); Intrinsic; Postrenal
a) What are the most common causes of prerenal AKI? (4)
b) What are the 3 anatomical parts of the kidney involved in intrinsic AKI?
c) What are the 3 most common causes of damage to the tubules and interstitium?
d) What are the exogenous (6) and endogenous (4) types of nephrotoxins?
a) 1-Hypovalaemia, 2-Decreased CO, 3-Decreased effective circulating volume (CHF &/or Liver failure), 4-Impaired renal autoregulation (NSAIDS, ACEI/ARB, Cyclosporins)
b) Glomerulus (acute glomerular nephritis), Tubules and interstitium, Vascular (vasculitis, malignant hypertension, TTP-HUS)
c) Ischaemia, Sepsis/Infection, Nephrotoxins
d) Exogenous: Iodinated contrast, aminoglycosides, cisplatin, amphotericin B, PPIs, NSAIDs
Endogenous: Haemolysis, rhabdomyolysis, myeloma, intratubular crystals
a) What is the most common form of AKI and what are the conditions that cause it?
b) What occurs with prolonged periods of prerenal azotemia?
c) What is the significance of elevated Urea in AKI?
a) Prerenal azotemia is the most common form of AKI resulting in increased SCr &/or BUN due to inadequate renal plasma flow and intraglomerular hydrostatic pressure to support normal glomerular filtration. Commonly associated with hypovolaemia, decreased CO, and nephrotoxic medications.
b) Prolonged periods of prerenal azotemia may lead to ischemic injury- acute tubular necrosis (ATN).
c) Urea is a waste product formed in the liver when protein is broken down into amino acids. This process produces ammonia, which is converted into the less toxic waste product Urea. Nitrogen is a component of both ammonia and urea, so Urea and Blood Urea Nitrogen (BUN) are interchangeable. Urea is constantly filtered out of the kidneys and released into urine, therefore when eGFR decreases due to AKI, Urea levels increase in the blood.
a) What are the normal intrarenal mechanisms for maintaining perfusion pressure during hypovolemia in regards to afferent and efferent arteriole?
b) What is the effect of NSAID on this process?
c) What is the effect of ARBs on this process?
a) Normal glomerular capillary pressure is maintained with reduced perfusion pressure by afferent vasodilatation and efferent vasoconstriction.
b) Reduced perfusion pressure with an NSAID. Loss of vasodilatory prostaglandins increases afferent resistance; this causes the glomerular capillary pressure to drop below normal values and the GFR to decrease.
c) Reduced perfusion pressure with an ACE-I or ARB. Loss of angiotensin II action reduces efferent resistance; this causes the glomerular capillary pressure to drop below normal values and the GFR to decrease.
a) What percentage of CO goes to the kidneys?
b) What are the normal homeostatic responses to decreased effective circulating volume and what are the mediators of this reponse?
c) What is the basic function of angiotensin II?
a) Renal blood flow accounts for 20% of the CO.
b) Renal vasoconstriction, with salt and water reabsorption are homeostatic responses to decreased CO/circulating volume. Angiotensin II, norepinephrine and vasopressin (ADH) are the mediators of this.
c) Maintains glomerular filtration by causing renal efferent vasoconstriction, which maintains glomerular capillary hydrostatic pressure closer to normal
a) What reflex occurs within the afferent arteriole, leading to dilation in the setting of low perfusion pressure, thereby maintaining glomerular perfusion.
b) What intrarenal vasodilator prostaglandins are produced in reponse to low renal perfusion pressure?
c) How is the macula densa involved in maintaining glomerular filtration?
d) When do these regulatory mechanisms fail?
a) Myogenic reflex
b) Kallikrein and kinins, and possibly nitric oxide (NO) also increase to cause vasodilation of afferent arteriole in response to low renal perfusion pressure.
c) Macula densa (specialized cells within the distal tubule) detects decreases in solute delivery, this elicits dilation of the juxtaposed afferent arteriole to maintain glomerular perfusion, mediated, in part, by Nitric Oxide (NO)
d) Even in healthy adults, autoregulation fails when systolic BP falls below 80mmHg
a) What factors may affect the renal autoregulatory response, and how does this occur physiologically?
b) What is the risk of AKI in advanced liver disease?
a) Atherosclerosis, L-T HTN, and older age. These factors can lead to hyalinosis (thickening of arteriole walls by hyaline material) and myointimal hyperplasia (abnormal proliferation of smooth muscle in vascular wall) which both involve narrowing of arterioles and impaired renal afferent vasodilation.
NB: In CKD, afferent vasodilation may be at max capacity to maximise GFR response to reduced renal mass.
b) Advanced liver disease can exhibit a haemodynamic profile resembling prerenal azotemia in the setting of total body overload. Primary arterial vasodilation in the splanchnic circulation ultimately results in vascocontriction similar to that seen in hypovaemia. AKI can be triggered by volume depletion or spontaneous bacterial peritonitis.
a) Define type 1 hepatorenal syndrome and when there is a poor prognosis associated with this
b) Define type 2 hepatorenal syndrome
a) HRS-1 is defined by a doubling of sCr within 2/52 to >221umol (eGFR usually <20) without alternate cause (e.g. shock/nephrotoxics). Poor prognosis is seen when there is a persistance despite volume administration and WH of diuretics.
b) HRS-2 is a less severe form characterised by a less severe sCr rise and involes diuretic resistant (refractory) ascites.
NB: HRS and prerenal azotemia is difficult to differentiate just by observation of kidney function, LFTs will indicate if HRS is a factor. There is no cure from a hepatic perspective except port-systemic shunt/liver transplant.
a) What are the most common causes of intrinsic AKI in general?
b) What are the most common exact causes of intrinsic AKI (exogenous and endogenous)
a) Sepsis, ischaemia, and nephrotoxins (endogenous and exogenous)
b) Acute tubular Necrosis (ATN), Disseminated intravascular coagulation (DIC), HTN, Penicillin, PPI, thrombotic thrombocytopenic purpura/haemolytic-uremic syndrome (TTP-HUS), tubulointerstitial nephritis-uveitis (TINU).
a) What is the primary mechanism of AKI in the context of sepsis, what is a clinical sign of ATN?
b) What is the haemodynamic effect of sepsis?
c) Which part of the kidneys is particularly vulnerable to ischaemic damage and what are the causative factors?
d) When does ischaemia-associated AKI most commonly occur?
a) With sepsis, AKIs typically occur in the setting of haemodynamic collapse requiring vasopressor support. ATN may be assumed with the presence of tubular debris and casts in the urine.
b) Generalised arterial vasodilation-mediated by cytokines that upregulate NO synthase in the vasculature-leading to decreased BP and reduced kidney perfusion, thus reducing eGFR.
c) The outer medulla, because of the architecture of the blood vessels that supply oxygen and nutrients to the tubules. Enhanced leukocyte-endothelial interactions in the small vessels lead to inflammation and reduced local blood flow to the metabolically very active S3 segment of the proximal tubule, which depends on oxidative metabolism for survival.
d) In the context of limited renal reserve (e.g. CKD or older age) with co-existing sepsis, vasoactive or nephrotoxic drugs, rhabdomyolysis, or systemic inflammatory states e.g. burns and pancreatitis.
NB: There is low risk of severe AKI with reduced perfusion alone, even after total interruption of renal blood flow during suprarenal aortic clamping or cardiac arrest.
a) What are the risk factors for post-operative AKI?
b) What is the mechanism for AKI with Burns and Acute Pancreatitis?
c) What diseases of the microvasculature can lead to AKI due to ischaemia?
d) What diseases of the macrovasculature can lead to AKI due to ischaemia?
a) CKD, older age, Diabetes Mellitus, CHF, and emergency procedures.
b) Extensive fluid losses into the extravascular compartments (third spacing) of the body frequently accompany severe burns and acute pancreatitis. This causes severe hypovaemia and a systemic inflammatory response which may facilitate AKI.
c) Thrombotic microangiopathies (cocaine, certain chemotherapy agents, antiphospholipid antibody syndrome, radiation nephritis, malignant hypertensive nephrosclerosis, and TTP-HUS), scleroderma, and atheroembolic disease.
d) Renal artery dissection, thromboembolism, or thrombosis, and renal vein compression or thrombosis
a) What is the mechanism of AKI due to nephrotoxic substances?
b) What is the type of AKI that occurs with iodinated substances, what is the clinical course and how does it occur?
c) What are the other diagnostic agents implicated as a cause of AKI?
a) Extremely high blood concentration of circulating substances along the nephron where water is reabsorbed and in the medullary interstitium; this results in high-concentration exposure of toxins to tubular, interstitial, and endothelial cells.
b) Contrast Nephropathy is characterized by a rise in SCr beginning 24–48 h following exposure, peaking within 3–5 days, and resolving within 1 week.
Contrast nephropathy is thought to occur from: (1) Hypoxia in the renal outer medulla; (2) Cytotoxic damage to the tubules directly or via the generation of oxygen-free radicals (concentration of agent within the tubule is markedly increased); and (3) transient Tubule Obstruction with precipitated contrast material.
c) High dose gadolinium for MRI and PO Sodium Phosphate in bowel prep
a) Name the antibiotics associated with AKI and the toxic mechanism on the kidneys
a) -Vancomycin: When trough levels are high and in combination with other nephrotoxic ABs
- Aminoglycosides (e.g Gentamicin) cause tubular necrosis. Aminoglycosides are freely filtered across the glomerulus and then accumulate within the renal cortex, where concentrations can greatly exceed those of the plasma. AKI typically manifests after 5–7 days of therapy. Hypomagnesemia is a common finding.
-Amphotericin B: (Antifungal) Causes renal vasoconstriction from an increase in tubuloglomerular feedback as well as direct tubular toxicity mediated by reactive oxygen species. Clinical features include polyuria, hypomagnesemia, hypocalcemia, and nongap metabolic acidosis.
-Acyclovir: Can precipitate in tubules and cause AKI by tubular obstruction.
NB: AKI secondary to acute interstitial nephritis can occur as a consequence of exposure to many antibiotics;incl penicillins, cephalosporins, quinolones, sulfonamides, and rifampin.
a) Which chemotherapeutic agents are well known to be a risk for AKI?
a) -Cisplatin and Carboplatin: Accumulate in proximal tubular cells and cause necrosis and apoptosis.
- Bevacizumab: Causes proteinuria and hypertension via injury to the glomerular microvasculature (thrombotic microangiopathy).
NB: Other antineoplastic agents such as mitomycin C and gemcitabine may cause thrombotic microangiopathy with resultant AKI.
a) What are the endogenous compounds that can possibly cause AKI?
b) When can these compounds be released in increased amounts?
c) What is the mechanism in which the AKI occurs?
d) What is the endogenous compound affecting the kidney in Tumour Lysis Syndrome?
e) How do myeloma light chains affect the kidney?
a) Myoglobin, Haemoglobin, Uric acid, and Myeloma light chains.
b) Myoglobin can be released by injured muscle cells, and hemoglobin can be released during massive hemolysis leading to pigment nephropathy. Rhabdomyolysis is characterised by high myoglobin levels.
c) Intrarenal vasoconstriction, direct proximal tubular toxicity, and mechanical obstruction of the distal nephron lumen when myoglobin or hemoglobin precipitates with Tamm-Horsfall protein (uromodulin, the most common protein in urine-produced in the thick ascending limb of the LoH), a process favored by acidic urine.
d) Massive release of uric acid (hyperuricaemia) leads to precipitation of uric acid in the renal tubules and AKI
e) Direct tubular toxicity and by binding to Tamm-Horsfall protein to form obstructing intratubular casts. NB: Hypercalcemia, which can also be seen in multiple myeloma, may cause AKI by intense renal vasoconstriction and volume depletion.
a) What is the mechanism of glomerulonephritis for AKI?
b) Describe post-renal AKI and the pathophysiology?
c) Describe the functional or structural issues leading to post renal AKI
a) Diseases involving the glomerular podocytes, mesangial and endothelial cells can lead to AKI by compromising the filtration barrier and blood flow within the renal circulation. NB: ~5% of AKI are glomerular.
b) When normally unidirectional flow of urine is acutely blocked either partially or totally, leading to increased retrograde hydrostatic intratubular pressure and interference with glomerular filtration. Reductions in GFR are due to underperfusion of glomeruli and changes to glomerular ultrafiltration coefficient.
c) Bladder neck obstruction e.g. prostate disease, neurogenic bladder or therapy with anticholinergic drugs; obstructed IDC, blood clots, calculi and urethral strictures are common causes of postrenal AKI which impacts both kidneys.
NB: Unilateral obstruction unlikely to cause AKI unless CKD or reflex vasospasm in contralateral kidney.
a) What is the obvious factor to differentiate AKI from CKD?
b) Without the above knowledge, what imaging clues suggest CKD?
c) What are the Pathology/Urine features of Prerenal Azotemia, Sepsis associated AKI, Ischaemia assoc AKI, Rhabdomyolysis, Haemolysis, Tumour Lysis and Multiple Myeloma?
a) A recent sCr baseline that shows normal kidney function would indicate an AKI.
b) Small, shrunken kidneys with cortical thinning on renal USS, renal osteodystrophy (done disease), normocytic anemia (with absence of blood loss or secondary hyperparathyroidism) with hyperphosphatemia and hypocalcemia, are consistent with CKD
c) -Prerenal Azotemia: BUN/Creatinine ratio >20, hyaline casts in urine, SG >1.018, UOsm >500
- Sepsis Assoc AKI: +ve MCS, renal tubular epithelial casts, often granular casts
- Ischaemia Assoc AKI: Granular casts, renal tubular epithelial casts
- Rhabdomyolysis: Elevated myoglobin, CK; urine haem positive with few RBCs
- Haemolysis: Anemia, elevated LDH, low haptoglobin
- Tumour Lysis: Hyperphosphatemia, hypocalcemia, hyperuricemia
- Multiple Myeloma: Monoclonal spike in urine or serum electrophoresis; low anion gap; anemia
a) What symptoms and history may increase clinical suspicion for AKI?
b) What objective physical signs may indicate/high suspicion of AKI?
c) What medical conditions may give rise to AKI if exacerbated?
d) What conditions may increases suspicion of post renal AKI?
e) What is an important consideration for medications in AKI aside from the nephrotoxicity?
d) What findings would indicate a Glomerulonephritis as apossible cause for AKI?
e) What miscellaneous conditions should also be a consideration for AKI?
a) Vomiting, diarrhoea, glycosuria causing polyuria, medications including diuretics, NSAIDS, ACEI & ARBs.
b) Orthostatic hypotension, tachycardia, reduced JVP, decreased skin turgur and dry mucous membranes
c) CHF, Liver disease, nephrotic syndrome, vascular disease (possible renal artery disease)
d) Prostatic disease, nephrolithiasis, pelvic/para-aortic malignancy
e) Doses of certain medications must be adjusted for reductions in kidney function. NB: sCr increases will lag behind changes in filtration rate.
d) Palpable purpura, pulmonary haemorrhage, or sinusitis raises the pssibility of systemic vasculitis with glomerulonephritis.
e) AKI in a person with hx of autoimmune disease such as systemic lupus erythematosus should lead to consideration of exacerbation of underlying disease. Pregnancy should also lead to consideration of preeclampsia as the cause of AKI. Tense abdomen should prompt consideration of abdominal compartment syndrome etc
a) What situations could cause complete anuria?
b) What urine output has a worse prognosis?
c) What diagnosis should be considered with red or brown urine?
d) What diagnosis can be considered depending on the proteinuria found in urine sediment examination?
a) Complete urinary tract obstruction, renal artery occlusion, sptic shock, severe ischaemia (with cortical necrosis), or severe proliferative glomerulonephritis or vasculitis.
b) Oliguria AKA reduction in UO denotes more severe AKI
c) Pigment nephropathy due to haemolysis causing Rhabdomyolysis.
d) AKI from ischaemia or nephrotoxins leads to mild proteinuria. Greater proteinuria in AKI suggests damage to glomerular ultrafiltration barrier or excretion of myeloma light chains (NB: Myeloma light chains are not detected in urine dipstik [albumin] and need sulfosalicylic acid test or immunoelectrophoresis). Heavy proteinuria is present in glomerulonephritis, vasculitis, or toxins/medications that affect glomerulus+tubulointerstitium (e.g. NSAIDs).
NB: AKI can complicate minimal change disease (a cause of nephrotic syndrome). If dipstik is +ve for haemoglobin but few red cells are evident in urine sediment, then rhabdomyolysis or haemolysis should be suspected.
a) What is the characteristic urine sediment findings in the following diagnosis?
- ATN due to ischaemic injury/sepsis/nephrotoxins:
- Glomerulonephritis:
- Interstitial Nephritis:
b) What diagonsis should be considered with the finding of Oxalate crystals or Uric acid crystals?
a) -ATN due to ischemic injury, sepsis, or certain nephrotoxins: Pigmented “muddy brown” granular casts and tubular epithelial cell casts (may be absent in 20% of cases)
- Glomerulonephritis may lead to dysmorphic red blood cells or red blood cell casts.
- Interstitial nephritis may lead to white blood cell casts.
NB: Urine sediment findings overlap in glomerulonephritis and interstitial nephritis, Dx not possible with urine sediment alone.
b) Oxalate crystals in AKI should prompt an evaluation for ethylene glycol toxicity. Abundant uric acid crystals may be seen in the tumor lysis syndrome.
a) What is the pattern of sCr rise with Prerenal Azotemia, Contrast nephropathy, Atheroembolic disease and toxins such as aminoglycosides ABs and Cisplatin?
b) What pathology tests are helpful for the Dx of glomerulonephritis and vasculitis?
a) -Prerenal Azotemia: Modest rises in SCr that return to baseline with improvement in hemodynamic status.
- Contrast nephropathy leads to a rise in SCr within 24–48 h, peak within 3–5 days, and resolution within 5–7/7
- Atheroembolic disease usually manifests with more subacute rises in SCr, although severe AKI with rapid increases in SCr can occur in this setting.
- Aminoglycoside antibiotics and cisplatin, the rise in SCr is characteristically delayed for 3–5 days to 2 weeks after initial exposure.
b) Depressed complement levels and high titers of antinuclear antibodies (ANA), antineutrophil cytoplasmic antibodies (ANCAs), antiglomerular basement membrane (anti-GBM) antibodies, and cryoglobulins.
a) What are the causes of disproportionate BUN elevation in comparison to sCr?
b) Describe the FeNa?
c) What can affect the FeNa?
d) When is FeNa >1% and when is it <1%?
a) Low tubular flow rate and increased renal medullary recycling of urea seen in prerenal azotemia causing AKI, however other causes include upper gastrointestinal bleeding, hyperalimentation, increased tissue catabolism, and glucocorticoid use.
b) The fraction of the filtered sodium load that is reabsorbed by the tubules, and is a measure of both the kidney’s ability to reabsorb sodium as well as endogenously and exogenously administered factors that affect tubular reabsorption.
c) Sodium intake, effective intravascular volume, GFR, diuretic intake, and intact tubular reabsorptive mechanisms.
d) FeNa is frequently >1% because of tubular injury and resultant inability to reabsorb sodium. FeNa <1%, suggests avid tubular sodium reabsorption.
a) In post-renal AKI, what imaging can be considered to investigate possible obstruction? What findings may be apparent in the presence of obstruction?
b) What are the differences in kidney size in terms of acute v CKD?
c) When is renal biopsy considered?
d) What main biomarkers are available for use in the clinical setting?
a) Renal USS or CT-KUB. Dilatation of the collecting system and hydroureteronephrosis.
b) In CKD, kidneys are usually smaller (unless patient has diabetic nephropathy, HIV-assoc nephropathy, or infiltrative diseases). Normal sized kidneys are expected in AKI. Enlarged kidneys in a patient with AKI suggests the possibility of acute interstitial nephritis or infiltrative diseases.
c) When prerenal azotemia, postrenal AKI, and ischemic or nephrotoxic AKI are deemed unlikely, and other possible diagnoses are being considered such as glomerulonephritis, vasculitis, interstitial nephritis, myeloma kidney, HUS and TTP, and allograft dysfunction.
d) Kidney injury molecule-1 (KIM-1) is a type 1 transmembrane protein that is abundantly expressed in proximal tubular cells injured by ischemia or nephrotoxins such as cisplatin.
Neutrophil gelatinase associated lipocalin (NGAL, also known as lipocalin-2 or siderocalin). is highly upregulated after inflammation and kidney injury and can be detected in the plasma and urine within 2 h of cardiopulmonary bypass–associated AKI.
a) What are some general complications of severe AKI?
a) -Uraemia: At high concentrations, mental status changes and bleeding complications can arise.
-Hyponatraemia (fluid O/L)
-Hyperkalaemia: Common in rhabdomyolysis, hemolysis, and tumor lysis syndrome due to release of intracellular potassium from damaged cells.
-Metabolic Acidosis (usually with elevated anion gap) can complicate acid-base & potassium balance.
-Bleeding: Direct hematologic effects from AKI-related uremia include decreased erythropoiesis and platelet dysfunction.
-Cardiac Complications: Arrhythmias, pericarditis, and pericardial effusion. Volume overload and uremia may lead to impaired cardiac function.
-Malnutrition: AKI is often a severely hypercatabolic state, therefore malnutrition is a major complication.
-Infection: Impaired host immunity has been described in end-stage renal disease and may be operative in severe AKI.
Hyperphosphataemia and Hypocalcaemia: Hyperphosphatemia, in highly catabolic patients or those with AKI from rhabdomyolysis, hemolysis, and tumor lysis syndrome. AKI-associated hypocalcemia can arise from derangements in vit D–parathyroid hormone–fibroblast growth factor-23 axis. Hypocalcemia is often asymptomatic but can lead to perioral paresthesias, muscle cramps, seizures, and prolongation of the QT interval.
-Hypervolaemia & Hypovolaemia: Expansion of extracellular fluid volume due to impaired salt and water excretion. The result can be weight gain, dependent edema, increased jugular venous pressure, and pulmonary edema; the latter can be life threatening. Recovery from AKI can sometimes be accompanied by polyuria, which, if untreated, can lead to significant volume depletion.
a) What are the 4 main considerations when treating an AKI?
b) What is the acute treated for AKI due to Glomerulonephritis/Vasculitis, allergic interstitial nephritis, scleroderma (scleroderma renal crisis), rhabdomyolysis or idiopathic TTP-HUS?
a) Optimisation of Haemodynamics, correction of fluid and electrolyte imbalances, discontinuation of nephrotoxic medications, and dose adjustment of administered medications.
b) -Glomerulonephritis/ Vasculitis: Immunosuppressive agents &/or plasmapheresis
- Allergic interstitial nephritis: (due to meds) Cease offending meds.
- Scleroderma (scleroderma renal crisis): ACE Inhibitors
- Idiopathic TTP-HUS: Plasma exchange (medical emergency). Pharmacologic blockade of complement activation may also be effective.
- Rhabdomyolysis: Aggressive volume repletion (up to 10L p/day). Plus diuretics if needed to achieve urinary flow rates of 200–300 mL/h.
NB: No specific therapy for rhabdo other than dialysis (severe) or supportive care with fluid and electrolyte balance & tissue perfusion. Pay attention to calcium and phosphate because of precipitation in damaged tissue and release when tissue heals.
a) What are the treatment options for post renal AKI?
a) Prompt recognition and relief of urinary tract obstruction.
- Transurethral or suprapubic bladder catheterization may be needed for urethral strictures or functional bladder impairment.
- Percutaneous nephrostomy tube placement or ureteral stent placement for ureteric obstruction.
a) What are the main supportive measures for AKI?
b) What acid/base imbalance is associated with an AKI and when do you treat these?
c) What electrolyte imbalance is assoc with AKI and how is it treated?
d) What is the mechanism and treatment for AKI related malnutrition and anaemia?
a) -IVF (NB: Hypervolemia in oliguric or anuric AKI may be life threatening due to APO)
- In severe cases of volume overload, furosemide may be given w/wo thiazide diuretic.
- Fluid and Na restriction
b) Metabolic Acidosis is assoc with AKI. Not treated unless severe (pH <7.20 and serum bicarbonate <15 mmol/L). Can be treated with oral or intravenous sodium bicarbonate
c) Hypocalcaemia and Hyperphosphataemia, the latter can be rx by limiting instestinal absorption with phosphate binders (calcium carbonate, calcium acetate, aluminium hydroxide). Hypocalcaemia does not usually require therapy unless symptoms are present.
d) Inadequate nutrition may lead to starvation ketoacidosis and protein catabolism. Excessive nutrition may increase the generation of nitrogenous waste and lead to worsening azotemia. Patients with AKI should achieve a total energy intake of 20–30 kcal/kg per day.
Anaemia in AKI is multifactorial and does not respond to erythropoiesos-stimulating agents. Prophylaxis for GI bleeding (due to uremia) with PPI may be required, however PPI have been associated with interstitial nephritis.
a) In general, when is dialysis considered?
b) When to start dialysis is still a debate, what are the pros/cons of starting early vs late?
c) At what uremic value do some nephrologists start dialysis and what are the available dialysis modes?
d) What are the different types of dialysis?
a) When medical management fails to control overload, hyperkalaemia, or acidosis; also if there is the presence of severe complications of uremia (asterixis, pericardial rub/effusion, encephalopathy, uremic bleeding).
b) Late initiation= risk of volume, electrolyte, and metabolic complications of AKI. -Initiating early: Unnecessary exposure to IV lines and invasive procedures, with risks of infection, bleeding, procedural complications, and hypotension.
c) When BUN >35mmol/L. Modes for renal replacement therapy (RRT) are via the peritoneal cavity (for peritoneal dialysis) (not commony usd for AKI) or the large blood vessels (for hemodialysis, hemofiltration, and other hybrid procedures)
d) Hemodialysis is typically performed 3–4 h per day, three to four times per week, and is the most common form of renal replacement therapy for AKI. One of the major complications of hemodialysis is hypotension.
Continuous renal replacement therapy (CRRT) can be performed by convective clearance or diffusive clearance.
NB: Prerenal and post renal AKI have better overall outcomes that intrarenal AKI.
a) Describe the Glomerulus, where it resides, it’s attachments and it’s anatomy including important cells
a) The glomerulus resides within Bowman’s space.
- Lined by parietal cells that transition into tubular epithelia migrating to proximal nephron or to replace podocytes.
- Attached to afferent arteriole that forms a branching capillary bed in mesangial matrix, which funnels out to efferent arteriole.
- Fenestrated endothelial cells rest on a Glomerular Basement Membrane (GBM) which line glomerular capillaries.
- Delicate foot processes from podocytes cover the outer surface of glomerular capillaries, interconnecting with adjacent podocytes by slit-pore membranes forming a selective filtration barrier.
- Efferent arteriole carries blood into cortical peritubular capillaries aka medullary vasa recta that supply and exchange with a folded tubular architecture.
a) How can immune deposits affect the GBM?
b) What pathology tests can be done to indicate the above?
c) How are GBM damaged in this immune mediated process?
a) Preformed immune deposits collect along the GBM in the subendothelial space or in situ along the subepithelial space.
b) Immunofluorescent staining with labeled anti-IgG can demonstrate linear staining for anti-GBM disease or immune deposits with membranous glomerulonephritis
c) I_mmune deposits_ and complement deposition classically draw macrophages and neutrophils into the glomerulus incl. T lymphocytes. These locally derived oxidants and proteases expand inflammation. GBM are damaged with either endocapillary or extracapillary proliferation.
a) How may chronic Glomerulonephritis appear on USS KUB?
b) What are the common symptoms of a patient who is quickly developing renal failure?
c) What is the difficulty with Primary Glomerulonephritis that has progressed slowly?
a) Chronic glomerular disease often presents with decreased kidney size.
b) Fatigue, weakness, uremic symptoms assoc with nausea, vomiting, fluid retention, and somnolence.
c) Patients can be remarkably asymptomatic, as are patients with acute glomerulonephritis without much loss in renal function. Selected patients who are clinically stable, have adequate blood clotting parameters, and are willing and able to receive treatment are encouraged to have a renal biopsy.
a) What would the renal biopsy in poststreptococcal glomerulonephritis demonstrate?
a) Hypercellularity of mesangial and endothelial cells, glomerular infiltrates of polymorphonuclear leukocytes, granular subendothelial immune deposits of IgG, IgM, C3, C4, and C5–9, and subepithelial deposits (which appear as “humps”)
a) What is the gold standard for IgA diagnosis?
b) How does IgA nephropathy most commonly present?
c) What is the prognosis of IgA Nephropathy?
d) What is the treatment of IgA Nephropathy?
a) Renal biopsy, despite elevated serum IgA levels in 20–50% of patients, and IgA deposition in skin biopsies in 15–55% of patients.
b) Recurrent episodes of macroscopic hematuria during/immediately following an URTI. Often accompanied by proteinuria &/or persistent asymptomatic microscopic hematuria.
c) IgA nephropathy is a benign disease for the majority, and 5–30% go into a complete remission, with others having hematuria but well preserved renal function. In the minority, there is slow progressive disease, with renal failure seen in only 25–30% of patients over 20–25 years.
NB: Persistent proteinurea for >6 months have poorer outcomes.
d) Large studies have supported the use of ACE-I in patient with proteinuria or declining renal function. In patients with persistent proteinuria steroids and immunosuppressive therapies have shown conflicting results.
NB: When presenting as RPGN, patients typically receive steroids, cytotoxic agents, and plasmapheresis.
a) What is MEMBRANOPROLIFERATIVE GLOMERULONEPHRITIS (MPGN)?
b) How is it subdivided into types and what are the types?
c) Hw do patients with MPGN present?
d) What are the treatments?
e) What are the clinical signs of poor outcome?
a) An immune-mediated glomerulonephritis characterized by thickening of the GBM with mesangioproliferative changes; 70% of patients have hypocomplementemia.
b) Subdivided pathologically into type I, type II, and type III disease.
- Type I MPGN is commonly assoc with persistent hep C infections, autoimmune diseases like lupus or cryoglobulinemia, or neoplastic diseases. Type I is the most proliferative, shows mesangial proliferation with lobular segmentation on renal biopsy and mesangial interposition between the capillary basement membrane and endothelial cells, producing a double contour sometimes called tram-tracking.
- Types II and III MPGN can be idiopathic, and immunoglobulin-mediated disease (driven by the classical complement pathway).
c) Proteinuria, hematuria, and pyuria (30%); systemic symptoms of fatigue and malaise are most common in children with type I disease; or an acute nephritic picture with RPGN and a speedy deterioration in renal function in up to 25% of patients. Low serum C3 levels are common.
d) In the presence of proteinuria, treatment with inhibitors of the renin-angiotensin system is prudent. In secondary MPGN, treating the associated infection, autoimmune disease, or neoplasms is of benefit. In particular, pegylated interferon and ribavirin are useful in reducing viral load.
e) Nephrotic syndrome, hypertension, and renal insufficiency all predict poor outcome.
