Renal

Step-wise, to treat hyperkalemia,

 Give calcium gluconate to stabilize the cardiac cell membranes and prevent
arrhythmias.
 Determine the cause of the hyperkalemia.
 Utilize short-term pharmacotherapy (insulin + glucose, ß-agonists, sodium
bicarbonate) to shift K+ back into the intracellular environment
 Increase K+ excretion by giving normal saline with a loop diuretic, via a cation-exchange
resin like sodium-polystyrene or by hemodialysis.

Acute poststreptococcal glomerulonephritis (PSGN) can be confused with IgA nephropathy.

Although the presentation of PSGN is similar to that of IgA nephropathy, PSGN occurs 2–4
weeks after a group A streptococcal pharyngitis or skin infection. IgA nephropathy occurs
concurrently with or shortly after an upper respiratory tract infection. Granular or linear IgG
deposits can be seen in poststreptococcal glomerulonephritis. Deposition of IgM in the mesangial
matrix is nonspecific.

Gastric parietal cells continue to replace hydrogen ions, which are lost in the vomit, and as they
do so they continue to pump bicarbonate ions into the plasma. Initially, this excess bicarbonate
exceeds renal capacity for reabsorption and bicarbonate is lost in the urine, increasing urine
pH. However, after roughly 3 days, a maintenance phase occurs wherein renal bicarb
reabsorption capacity improves, urine bicarbonate decreases, and the urine becomes relatively
acidic despite continued alkalemia (paradoxical aciduria). Concurrently, volume depletion
activates the renin-angiotensin-aldosterone system, leading to renal sodium reabsorption and
potassium and hydrogen ion excretion. One would thus expect to find acidic urine with low
urine sodium (<20 mEq/L), as seen in this patient who is likely in the maintenance phase of her
metabolic alkalosis.

Acyclovir is generally well-tolerated; however, the drug can precipitate as crystals in the
glomerular tubules during excretion, causing tubular obstruction and local
inflammation. Inflammation leads to AKI that is manifested as decreased urine output, increased
BUN, and increased creatinine. Although acyclovir-associated AKI can occur with oral
administration of the drug, it occurs most commonly when the drug is given intravenously.
Adequate oral or IV hydration is the best method to prevent crystal-induced AKI. Other drugs
that cause this condition include protease inhibitors, methotrexate, and sulfonamides.
In patients with leukemia, when rapidly dividing cells die, they release large amounts of
phosphate and purines into the bloodstream. Purines are metabolized and eventually form
excess uric acid. The presence of these metabolites in high concentrations can result in acute
kidney injury.

One of the key methods of protecting patients’ kidneys from tumor lysis syndrome is the
administration of allopurinol (a drug also used in the treatment of gout) with chemotherapy.
This drug inhibits the enzyme xanthine oxidase, which is responsible for the final step of
converting purines to uric acid. Blocking uric acid synthesis reduces the load on the kidneys
and can prevent renal failure.

Zero-order elimination of a drug implies that the rate of elimination is constant regardless of
its plasma concentration, so that a constant amount of drug is eliminated per unit time. As a
result, the plasma concentration of the drug decreases linearly with time.

Phenytoin is one of a few drugs that follow zero-order elimination. Drugs with zero-
order elimination includePhenytoin, Ethanol, and high-dose Aspirin (mnemonic: PEA),
although this may vary under certain conditions.

Bethanechol, misoprostol, propanol, and rifampin all follow first-order elimination. This
means that the rate of elimination is proportional to the drug concentration so that a constant
fraction of drug is eliminated per unit time. As a result, the plasma concentration of these drugs
decreases exponentially with time. Most drugs follow first-order elimination at therapeutic
levels.

This question requires you to recognize that gluconeogenesis—and not glycogenolysis—is the
major contributor to renal glucose release and then to recall which enzyme is rate limiting in
gluconeogenesis (fructose-1,6-bisphosphatase).

This patient most likely has drug-induced acute tubulointerstitial nephritis (also known
as acute interstitial nephritis[AIN]), which manifests histologically as edema and inflammation
of the renal tubules and interstitium with sparing of the glomeruli.

AIN is most often associated with drug toxicity, such as dicloxacillin. Drugs that have been
associated with tubulointerstitial nephritis include sulfonamides (ie, Hydrochlorothiazide,
a thiazide diuretic), penicillins (ie, dicloxacillin), cephalosporins, ciprofloxacin, allopurinol,
proton pump inhibitors, rifampin, cimetidine, and nonsteroidal anti-inflammatory
agents. Withdrawal of the causative agent is the best treatment, but it may take months for a
patient to fully recover renal function.
AIN may also be caused by infections and autoimmune processes. Intrinsic renal diseases
present with a BUN:Cr ratio less than 10. Other common findings on urinalysis are sterile
pyuria, microscopic hematuria, andeosinophiluria.

This patient presents with loss of kidney function and biopsy findings suggestive of acute
rejection. Acute rejection can occur at any time but is most likely in the first 3 months after
transplantation. It is due to human leukocyte antigen discrepancies between host and graft
and is more common in highly vascular organs such as the liver or kidney. This often leads to
activation of cytotoxic T-cells (CD8), which will lead to lysis of graft cells and the production of
cytokines that will recruit other inflammatory cells. In the kidney, it manifests as acute
tubulitis.

The histology image shows cytotoxic T-cells (CD8) attacking the renal tubules, causing acute
tubulitis. The CD8 response recruits other inflammatory mediators as pictured. Additionally, if
this acute rejection included a humoral component then the biopsy would have demonstrated
vasculitis and intimal infiltration as well.

This table breaks down the differences between the possible types of transplant rejection:

 CD20 is a B cell marker. B cells are involved in hyperacute rejection as well as the
humoral type of acute rejection.
 CD27 is a marker of plasma cells. Plasma cells are involved in hyperacute rejection.
 CD34 is a marker of fibrocytes, which are involved in chronic rejection.
 CD4 is a marker of helper T cells. While helper T cells do play some role in acute
rejection, the image depicts the cytotoxic (CD8) response. Helper T cells are also
involved in chronic rejection.
 CD56 is a marker of natural killer cells. Natural killer cells are involved in hyperacute
rejection.

Loop diuretics may be used to treat hyperkalemia because they increase the excretion of
potassium. Hyperkalemia is a serious condition because of the possibility of developing an
arrhythmia. Patients should be treated when ECG changes are present (spiking of the T wave)
or when serum potassium reaches =7.0 mEq/L. Initial treatment may include calcium, which
will antagonize the membrane actions of excess potassium to help prevent an arrhythmia,
along with insulin and glucose, which help to pull potassium from outside to inside the cell. The
patient may also receive sodium polystyrene (Kayexalate), a gastrointestinal syrup that works
more slowly by ridding the body of potassium through the stool.

the loading dose of a medication should remain the same as for other patients because it is
dependent on the volume of distribution, not excretion or metabolism. The maintenance dose,
on the other hand, should be decreased to account for less effective clearance. Because
fluoroquinolones are excreted renally and because this patient has chronic renal insufficiency,
the maintenance dose should be lowered in this case. This can be accomplished either by
reducing the dose of the medication or the frequency of administration.

The loading dose is dependent on volume of distribution, not renal excretion.

Therefore increasing or decreasing the loading dose would not be appropriate. On the other
hand, the maintenance dose is dependent on renal excretion so increasing or maintaining the
same maintenance dose would lead to accumulation of the drug in the blood.

This patient’s decreased urine output, azotemia, and acute increase in serum creatinine in the
setting of liver disease raise concern that he may be experiencing hepatorenal
syndrome. Hepatorenal syndrome is a progressive functional renal failure caused by a
reduction in the glomerular filtration rate due to declining liver function. It is characterized by
splanchnic vasodilation and concomitant vasoconstriction in the renal vascular beds caused by
the production of mediators and the activation of the renin-angiotensin-aldosterone system.
The combination of these two factors causes a prerenal type of azotemia, evidenced by the
patient’s blood urea nitrogen/creatinine ratio > 21 and a fractional excretion of sodium (FeNa)
of 0.3%.

One of the features of hepatorenal syndrome is that kidney anatomy is completely unaffected,
and thus visualization of the kidneys by most modalities would reveal normal size and
shape.

Normal kidneys with a “flea-bitten” infarcted appearance are characteristic of patients with
malignant hypertension.

This patient with myalgias, urinary frequency, and myoglobinuria has been consuming large
quantities of grapefruit juice. In the context of statin use, these signs and symptoms point to a
diagnosis of acute tubular necrosis as a result of rhabdomyolysis.

Rhabdomyolysis is an adverse effect of statins, many of which are metabolized by cytochrome

P-450 enzymes. Grapefruit juice inhibits P-450, thereby slowing metabolism of the statin. This
results in higher concentrations of the drug and increased risk of rhabdomyolysis. Patients who
take higher doses of statins are already at increased risk for rhabdomyolysis.

Rhabdomyolysis is characterized by the breakdown of muscle tissue; myoglobin released by

the muscles is toxic to kidney tubule cells, especially in the proximal tubule. In the image
shown, all of the tubules are necrotic, with sloughed pink epithelial cells, debris, and loss of
nuclear detail. Although ATN is is commonly associated with oliguria, it frequently manifests
with increased urine output (in 50% of patients), as seen in this scenario.