DIALYSIS

Mechanical kidneys

Dialysis Machines are artificial kidneys. These are large (and expensive) machines. They allow patients to artificially urinate. Fluid is taken from the body, “pee” is filtered out, then clean fluid is returned. It’s similar to cardiopulmonary bypass, except for peepee. There are three kinds of dialysis.  

1. Hemodialysis -  this is the most common kind of dialysis. Must be performed in a dialysis center (or hospital). Each session takes half a day. Requires 3 sessions per week. Needles are inserted into a “shunt” on the patient’s arm, and their blood is filtered.

2. Peritoneal Dialysis - this machine is much cheaper, because it cleverly uses peritoneal fluid instead of blood, and peritoneal fluid requires a lot less filtration. Needles are inserted into the belly. The upside is that the machine can be brought home and run overnight. Only responsible patients are allowed to use it, since peritoneal infections are bad. Also, and this isn’t in textbooks, ESRD patients are notoriously irresponsible. After all, most of them got to this point by being non-adherent with their diabetic or HTN treatment. That’s an overgeneralization, though there’s some truth behind it.  

3. Hemofiltration - reserved for really sick patients. They’re labwork is changing so fast that the usual “3 sessions per week” schedule ain’t sufficient. Instead, their blood is constantly filtered at a slow pace. The slow pace allows for sophisticated maneuvering by the nephrologist. 

Vascular Access - it makes a big difference where you put the needle. The size of the vein determines the speed of the dialysis session. A big vein means a quick session. 

1. Central Line - in an emergency, nephrologists can use a central line (subclavian, femoral or jugular vein) each time they dialyze someone. But central lines have a 1% complication rate (infection, clotting, restenosis). Instead, ESRD patients deserve a more permanent solution….

2. Fistula (Shunt) - surgically creating an AV fistula may seem dumb, but it dramatically improves vascular access for those undergoing routine dialysis. Shunts are just durable! They’re almost always placed in the arm. A surgeon fuses an artery and vein together. A few months later, the shunt is ready. The resultant fistula is really easy to stick with a needle, and has really low complication rates. On the physical exam, you can auscultate the shunt to investigate its patency. Open shunts make a “thrill” or whoosh sound. 

Indications for Dialysis in patients with stage 5 CKD 

Acidotic

Electrolyte abnormalities (especially hyperkalemia)

Intoxication of dialyzable drug (ASA, Lithium, Ethylene Glycol, Iso Alcohol, Mg Laxatives)

Overload of fluid (they’re swollen)

Uremic symptoms (too uncomfortable)

PRE-RENAL AKI

Hypoperfusion

Pre-Renal AKI is due to poor circulation to the kidney. Usually dehydration or shock. 

If there’s less blood flow, then inherently there is going to be less filtration occurring across the glomerulus -- hence the low GFR. And if filtration is decreased at the beginning of the nephron, then obviously the output of urine at the end of the nephron will be low (oliguria). 

As fluid flows through the nephron, it’s important to know how the BUN and Cr behave. BUN can be resorbed, but Cr cannot. That’s why the serum BUN rises more than the serum Cr. In a healthy person, the ratio is usually 15:1. But in Prerenal AKF, the starving nephrons pull the RAAS alarm, which leads to increased reabsorption of water (and BUN) in the distal nephron. So patients with Prerenal AKF have their serum BUN levels “supercharged” without any modification of the Cr. BUN:Cr > 15. A few other lab tests, like FENa and Urine Osmolality will be normal, since those tests evaluate tubular function. 

If hypoperfusion goes on long enough, eventually the nephron cells will die. At that point, we call it Acute Tubular Necrosis, which is a type of Intra-Renal AKI. A bit confusing, I know. But in my experience, test questions are usually abundantly clear here.

*Side note - Tacrolimus is a nephrotoxic cancer drug. Unlike most nephrotoxic drugs, its mechanism is pre-renal.

POST-RENAL AKI

Obstruction

Post-Renal AKI is due to blocked urine. It’s usually due to kidney stones, tumors or a big prostate. The pressure builds up in the kidney (hydronephrosis) and its tubules. That pressure limits the GFR. And that causes Azotemia. 

Early on, the BUN:Cr ratio will be high (over 20), because the tubules haven’t died yet. Later, the high pressure eventually kills the renal tubular cells. That results in little-to-no BUN resorption (similar to Intra-Renal AKI), and the BUN:Cr ratio falls below 15. And now that the tubular cells are dead, the FENa rises over 2%, and the urine becomes diluted (failure to concentrate). 

Here’s a tidbit about the prostate. The urine flows through the center of the prostate. In prostate cancer, the tumor usually grows on the periphery of the prostate, leaving urine flow untouched. But in benign prostate hypertrophy (BPH), the prostate growth is uniform, which squishes the flow of urine. 

Kidney stones usually don’t cause post-renal AKI in a healthy person because the unaffected kidney can compensate for it. But in people with only one kidney, a stone can cause AKI. 

Explanation of Labwork in ATN

Plug formation → GFR is low → can’t filter BUN or Cr → Azotemia

Tubular epithelial cell death → Reabsorption of BUN is impossible → BUN / Cr ratio is low (less than 15)

Tubular epithelial cell death → K+ excretion is impossible → Hyperkalemia

Tubular epithelial cell death → Organic acid excretion is impossible → Anion Gap Metabolic Acidosis

Tubular epithelial cell death → Muddy brown or Granular epithelial casts (pathognomonic)

NaK Pump Polarity reversal → FENa is high (more than 2%)

Urine Output is variable. It’s low initially, then high during recovery.

AIN can progress to Renal Papillary Necrosis. The papillae have especially small arteries, making them vulnerable to ischemia. RPN produces gross hematuria (which is unusual in kidney problems), flank pain and sometimes a fever. The most common cause is NSAID use, but other potential causes are sickle cell disease, sickle cell trait, infection, inflammation or obstruction. 

RENAL TUBULAR DEFECTS

Highlighting normal nephron physiology

Fanconi Syndrome is when the proximal convoluted tubule breaks. The PCT reabsorbs a lot of wonderful molecules like glucose, amino acids, phosphate and bicarbonate. Without these building blocks, growth retardation and rickets will occur. Without bicarbonate, metabolic acidosis will occur (non-anion gap). Fanconi Syndrome has many unusual causes, including inherited mutations, heavy metal disorders (Wilson disease, lead, platinum drugs), sugar disorders (Glycogen storage disorders, Fructose intolerance) and amino acid disorders (Tyrosinemia). 

Bartter Syndrome is when the thick ascending limb of the loop of Henle breaks. It’s like taking a loop diuretic. The thick ascending limb reabsorbs water, sodium, potassium and chloride. Bartter Syndrome results in hypokalemia plus a metabolic alkalosis (see metabolic alkalosis page). The customer barttered for a pair of loop earrings. 

Gitelman Syndrome is when the distal convoluted tubule breaks. It’s like taking a thiazide diuretic. The DCT helps you reabsorb sodium, chloride and water, while getting rid of calcium. Gitelman leads to contraction alkalosis and hypercalcemia, but it is overall milder than Bartter and Fanconi. 

Liddle Syndrome is when the principal cells of the collecting duct are overactivated when their sodium channels (ENaC) become invincible to degradation. It’s similar to hyperaldosteronism, except the serum levels of aldosterone are low. Aldosterone raises the blood pressure at the expense of losing potassium. It also creates a metabolic alkalosis. The treatment is aimed at blocking the overactive ENaC channels with Amiloride or Triamterene.

Type 2 RTA occurs in the proximal convoluted tubule. The PCT can’t reabsorb bicarb. Patients pee out all of their basic bicarbonate, leaving their blood more acidic. It’s less severe than type 1 because the downstream α-intercalated cells can still acidify the urine. Because of this watering-down effect, the urine anion gap is normal. 

Type 4 RTA occurs when aldosterone is low. It’s not a true ion channelopathy. Without aldosterone, the principal cells are unable to make the compensatory acid NH3 (the reason for this is a bit complicated, so I’ll omit it). This is the only RTA where the serum potassium is high (because aldosterone is low).