6. Nephrology




Being stranded in the middle of a vast ocean is life’s biggest irony of eventual death—being surrounded by water everywhere, but to die due to lack of water.


This happens because our kidney’s concentrating ability is limited. For every liter of ocean water that we drink, an additional 1/2 liter of freshwater is needed to excrete the total salt load consumed. Rodents’ kidneys have more than 2 times the concentrating ability of humans’, hence they can survive on salty sea water.



6.1 Irritative and Voiding Symptoms


























Irritative symptoms


Voiding symptoms


Something is irritating the bladder wall or urethra causing inflammation. This results in:




  • Dysuria and resulting hesitancy



  • Frequency, urgency (irritated smooth muscles of kidney are contracting frequently)


Something in bladder is obstructing the urinary outflow, leading to dribbling of urine, sensation of incomplete voiding, and/or needing to strain to urinate.




  • Additional symptoms may include incontinence and nocturia (due to full bladder and incomplete voiding)


Causes:




  • Stones



  • Infection (prostatitis, cystitis, urethritis, etc.)



  • Tumor in the urinary tract


Causes:




  • Benign prostatic hyperplasia (BPH; most common cause of voiding symptoms in male)



  • Prostatic carcinoma



  • Acute prostatitis (inflammatory swelling)



  • Stone that is lodged in the neck of the bladder



  • Tumor in the neck of the bladder


Common causes: Stone, infection and tumor (MRS SIT)a


NSIDx is urinalysis (UA)


For recent onset of symptoms,NSIDx – UA.


For chronic symptoms




  • In males, think prostate first. So NSIDx is digital rectal exam, UA and serum prostate-specific antigen



  • In females, consider pelvic floor dysfunction


aThese can also cause hematuria.



In a nutshell

Irritative and voiding symptoms are collectively called “lower urinary tract symptoms” and have significant overlap:




  • Acute prostatitis can present with acute irritative and voiding symptoms.



  • Tumor in the neck of bladder can present with chronic irritative and voiding symptoms.



  • Patients with BPH have increased risk of urinary tract infection. In this case, a patient with longstanding hx of voiding symptoms, now presents with acute irritative symptoms due to development of cystitis or prostatitis.



6.2 Urinary Tract Infection and Prostatitis



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Acute onset irritative symptoms (frequency, urgency, hesitancy, and/or dysuria) +/- systemic signs of infection


Condition


+ Urethral discharge (in women also look for cervical tenderness)


Urethritis (STD)- see STD section in ID chapter


+ prostate tenderness


Prostatitis (generally patients with acute bacterial prostatitis have signs of sepsis with spiking fevers; presentation is NOT subtle)


No urethral discharge
No flank pain and no costovertebral angle (renal area) tenderness


• Cystitis (look for suprapubic pain or tenderness)
OR
Urethritis (sometimes urethritis does not have urethral discharge)


+ renal-angle tenderness and/or flank pain


Acute pyelonephritis (generally patients have signs of sepsis)



Urinalysis


In patients presenting with acute irritative symptoms, first SIDx is always urinalysis (UA).





















UA findings


Additional info


Pyuria = inflammation in the urinary tract


Definition
WBC ≥ 3 – 6/hpf (high-powered field) in unspun sample
WBC ≥ 10/hpf in centrifuged urine sample


Leukocyte esterase


When WBCs are present, urine leukocyte esterase will also be positive


Positive nitrites = presence of Enterobacteriaceae in urine


Enterobacteriaceae can change nitrates to nitrites (E. coli is the most common cause)
If nitrites are negative, but patients have pyuria consider infection with Staphylococcus epidermidis, enterococcus, S. saprophyticus, or STD (chlamydia and gonorrhea). These organisms cannot change nitrates to nitrites


Urinary tract infection (UTI) may also cause hematuria (RBCs ≥ 3/hpf in unspun sample)



6.2.1 Acute Cystitis


Presentation: acute irritative symptoms (+/- voiding symptoms). Older patients can have mild confusion. UA will show significant pyuria.



Management


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aNot recommended in patients with CrCl <60 mL/min.


bUnlike levofloxacin, moxifloxacin has poor penetrance into urinary tract and is not used for UTI.



Clinical Tip: Urine culture should be performed in all men with suspected acute UTI, even if uncomplicated.



Asymptomatic Bacteriuria

Definition: Significant colony counts of bacteria in urine culture (i.e., ≥ 105 cfu/mL) but with no irritative bladder symptoms or systemic signs of infection.


Rx: Antibiotics are indicated only in pregnancy or in patients who are undergoing urological procedure likely to have mucosal bleeding.



6.2.2 Acute Complicated UTI (including Pyelonephritis) and Acute Prostatitis


Definition: UTI + signs of extension beyond bladder e.g., fever, chills, rigors, sepsis, costovertebral angle tenderness, flank pain, acute creatinine elevation, altered mental status.


Risk factors for extension: uncontrolled diabetes, immunosuppression, urinary stones, urinary tract abnormalities, presence of indwelling structures (e.g., Foley catheter, urinary stent), pregnancy, etc.



Management


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aProstatic massage is contraindicated in suspected acute bacterial prostatitis, but it is ok to do a digital rectal examination to examine prostate.


bAcute elevation of PSA can support the dx of acute prostatitis.


cIn patients > 35 years old AND no hx of high-risk sexual behavior, use trimethoprim-sulfamethoxazole or a fluoroquinolone for a total of 6 weeks.



1 In sexually active patients with prostatitis <35 years of age, or >35 years of age with high risk sexual behavior, MCC are gonorrhea and chlamydia. For these patients, test for STD and initiate empiric treatment that covers these organisms.

MCC is E. coli. Note: trimethoprim-sulfamethoxazole and fluoroquinolones have good prostatic penetration.


dUrethral catheterization is contraindicated in acute bacterial prostatitis as this might lead to dissemination of infection.


eChoose empiric antibiotic therapy as following:




If risk factors for pseudomonas are present (e.g., recent urological instrumentation or neutropenia), use anti-pseudomonal antibiotic (e.g., cefepime, piperacillin-tazobactam).



If urine gram stain reveals gram positive cocci, cover for enterococcus and staphylococcus; can use piperacillin-tazobactam



If no hx of multi-drug resistant organism (e.g., MRSA, vancomycin resistant enterococci)



Otherwise, use IV ceftriaxone.


fIn very sick patients (e.g., ICU or step-down unit), add antibiotics with MRSA and ESBL coverage (e.g., IV vancomycin + meropenem).


gUse oral ciprofloxacin, levofloxacin (5–7 days), trimethoprim-sulfamethoxazole (7–10 days) or B-lactams such as cefpodoxime, cefdinir, amoxicillin-clavulanate (10–14 days).


hCT scan with IV contrast is the best test. When contraindicated (e.g., in pregnancy) do renal ultrasound. Look for pyelonephritis complications such as abscess or emphysematous pyelonephritis.



2 In emphysematous pyelonephritis imaging will reveal air in the renal parenchyma.

Risk factors for development of these complications include immunosuppression or DM. Treatment for both is percutaneous or surgical drainage and IV antibiotics. Severe cases may require nephrectomy.



6.2.3 Perinephric/renal Abscess


Source of infection: local infection (e.g., pyelonephritis), or hematogenous spread (e.g., Staph. aureus abscess due to infective endocarditis)


Presentation: history of pyelonephritis with no clinical improvement despite adequate treatment, with persistent flank pain and high-grade fever. Exam may reveal palpable abdominal mass. UA may reveal pyuria, but urine culture may be negative (when abscess is not communicating with urinary system).


Workup: CT scan with IV contrast is the best test. When contraindicated (e.g., in pregnancy), do renal ultrasound.


Rx: IV antibiotics (e.g., Piperacillin-tazobactam) and percutaneous drainage of abscess. Severe cases may require nephrectomy.



6.2.4 Chronic Prostatitis and its Differential Diagnosis


Presentation: chronic or recurrent irritative symptoms in males with or without voiding symptoms.



3 In patients with hematuria, do bladder cancer workup (urine cytology, CT scan and cystoscopy)

Workup:



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aPatients can also present with recurrent UTIs or recurrent bacteriuria of the same organism. Treatment is similar to acute bacterial prostatitis: use fluoroquinolone (ciprofloxacin or levofloxacin) or trimethoprim-sulfamethoxazole for total of 6 weeks.


bProstate may be mildly tender. Treatment includes a trial of empiric antibiotic therapy (e.g. ciprofloxacin) and alpha-1 blocker (e.g., tamsulosin). In sexually active males, rule out STD prostatitis and consider infection with atypical organism (chlamydia, mycoplasma, etc.). In patients with hematuria, do further urologic workup (including cystoscopy).


cIn patients with chronic irritative bladder symptoms of unknown cause, particularly in patients > 40 years of age, or in patients with persistent hematuria we must rule out urogenital cancer by doing cystoscopy and urine cytology.



Benign Prostatic Hyperplasia

Presentation: Older male patients presenting with chronic voiding symptoms. Patient may also have chronic mild urgency and frequency. Benign prostatic hyperplasia (BPH) alone usually does not cause dysuria.


Exam: Digital rectal examination may reveal firm, smooth enlargement of prostate gland; however, there is a poor correlation between prostate enlargement (by exam or transrectal US) and obstructive symptoms due to BPH. Workup: NSIDx is urinalysis, serum creatinine, and prostate-specific antigen (PSA) to screen for prostate cancer.



Step-wise management


Drug of choice is alpha-1 antagonist which act on smooth muscles. Tamsulosin is preferred, because it has fewer side effects than other drugs in this group. Prazosin and doxazosin (+ azosin) can be considered when patients have coexistent hypertension


If patient continues to have symptoms, NSIM: add a 5-alpha reductase inhibitor (inhibits conversion of testosterone to dihydrotestosterone). They act on the epithelial portion of prostate, and has been shown to reduce prostatic volume. For example, finasteride and dutasteride (+terides)


Transurethral resection of prostate is indicated, if symptoms do not improve significantly with medical management or patients develop complications (e.g., hydronephrosis, renal failure, recurrent infection.)



Prostate Cancer

Background: Most common cancer in males and second Most common cause (MCC) of cancer death in males. There is a familial predisposition.


Risk factors: Black men, family hx of prostate cancer, BRCA mutation, etc.


Screening: Routine screening via PSA is controversial. Informed decision-making process is recommended. Patients who opt to screen for prostate cancer can begin at age 50 years.



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Presentation: In most patients, prostate cancer is suspected when found to have high PSA levels or abnormal digital rectal examination. Symptoms, when present, are often due to metastatic disease, such as low back pain/bone pain or pathological fracture (especially around the lumbar vertebra region).


Prostate exam: This may reveal indurated, nodular and/or irregular prostate enlargement.


Best SIDx: Prostate biopsy under transrectal ultrasound guidance.



Management

























Localized disease


Surveillance
or
Intervention with either prostate tissue ablation with radiationa or removal with surgeryb
Any of the above is acceptable. No studies have proven superiority of one over anotherc


Locally advanced disease or low-volume disseminated disease


Either prostate tissue ablation with radiation or removal with surgery + androgen depriving therapyd


Disseminated disease (high-volume disease)


Docetaxel (chemotherapy)
+
Androgen depriving therapy


aExternal beam radiation or radioactive pellets implantation into prostate.


bMost common side effects of surgery are erectile dysfunction and urinary incontinence.


cIn patients with high-risk features, prostate tissue ablation or removal may be offered.


dProstate cancer is an androgen-dependent cancer, so decreasing androgen production will shrink the tumor. This can be achieved by either removing both testicles (surgical orchiectomy) or by using medical therapy to decrease androgen production (as shown below).



Medical antiandrogen therapy


















GnRH agonist: leuprolide, goserelin,a nafarelin, etc. (+ relins)


Mechanism of action: Continuous stimulation by GnRH paradoxically results in downregulation of androgen production
• In initial phase, it may increase production of androgens, so androgen receptor antagonist, such as flutamide or bicalutamide, are used for short term to prevent initial androgen-mediated flare-up (+ tamides)


GnRH antagonist, e.g., degarelix


No increase in production of androgens in the initial phase


aGoserelin – Gonadotropin Inhibitor


Abbreviation: GnRH, gonadotropin-releasing hormone



MRS

Goin–Goin



Bladder Cancer

Risk factors: Phenacetin-containing analgesics, pioglitazone (possible), ethanol, smoking, Schistosoma haematobium (parasitic infection), aniline dyes, arsenic exposure, cyclophosphamide (chemotherapy).



MRS

PEE SAC cancer


Presentation: Painless gross or microscopic hematuria. Patients may also have chronic or inter-mittent-and-recurrent, irritative, and/or voiding symptoms.



Workup



  • NSIDx is office-based cystoscopy with biopsy (most appropriate diagnostic step) + urine cytology.



  • After confirming dx, NSIM is transurethral resection of bladder tumor (requires anesthesia), and CT/MRI scan with IV contrast for staging.



Screening is not recommended for bladder cancer; even in patients with risk factors.



Treatment


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Urinary Tract Stones

Presentation: Depends upon location of stone and complication (stones → obstruction → urine stasis → infection).



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Management of Suspected Urinary Tract Stone



  • If patient is in pain, First SIM is adequate hydration and analgesia (the choice of analgesia is nonsteroidal anti-inflammatory drugs [NSAIDs]).



    4 First step is always to control pain before doing further diagnostic test.

    Opiates are given when NSAIDs fail to control pain or when NSAIDs are contraindicated (e.g., renal failure). Opiates may exacerbate nausea/vomiting, which is common in renal/ureteral colic.



  • NSIM is UA (best initial test): symptomatic stones usually present with hematuria. Alkaline pH (pH > 7.5) may signal possible infection with urease-producing bacteria (e.g., Proteus, Klebsiella) and possibility of staghorn calculi. Urine pH < 5.5 may suggest uric acid stone.



  • • NSIDx is CT scan of abdomen and pelvis without IV contrast.



    5 Do not use contrast when looking for stones (or hemorrhage). Stones, blood, and contrast have similar high density appearance on CT. Using contrast will muddle the picture. For example, first diagnostic test in suspected stroke is CT scan of head without contrast. On the other hand, when looking for malignancy or infection use IV contrast. For example, first diagnostic test in a patient with fever and a new focal neurological deficit is CT scan of head with contrast.

    It has high sensitivity and specificity. In pregnant patients, do renal ultrasound, as CT scan is not desirable.



  • Hospitalization and urology evaluation is indicated in following situations:




    • Persistent significant pain, nausea, or vomiting (not controlled by oral medications).



    • Solitary kidney.



    • Sepsis.



      6 In septic patients with obstructive uropathy, urgent urology evaluation for decompression is indicated.




    • Creatinine elevation.


These patients frequently need emergent decompression, such as percutaneous nephrostomy or ureteral stent placement.



Further management of symptomatic urinary tract stone depends upon stone size, type, and location






























Size


Management (when urgent decompression is not needed)


≤ 0.5–1 cm


Stone of this size is expected to pass through. Use tamsulosin, which can facilitate stone passage
If stone does not pass spontaneously, consider intervention in patients with ongoing symptom


1 cm–2 cm renal (or ureteral) stone


Extra-corporeal shock wave lithotripsy (ECSWL)




  • It is contraindicated in pregnancy and bleeding disorders



  • It is commonly used for renal stones. It can also be used as a first-line treatment for small (< 1 cm) proximal ureteral stone


> 2 cm renal stone, or cystine stones, or stones in patients with urological anatomic abnormality (e.g., horse-shoe kidney)


Percutaneous nephrolithotomy (stone removal); this requires general anesthesia.




  • Bigger stones > 2 cm have higher risk of complications when broken down in situ with ECSWL and, cystine stones cannot be broken down by ECSWL



  • This can also be used for large, severely impacted proximal ureteral stones


Middle, distal (or proximal) ureter stone not passing through


Laser lithotripsy
+
ureteroscopic stone extraction


Laser lithotripsy helps to break down large stones which makes it easier to extract


Ureteroscope and cystoscope are both inserted through urethra; difference is that ureteroscope is more flexible and longer


Bladder stone not passing through


Laser lithotripsy
+
cystoscopic extraction



Always check stone composition after its removal or spontaneous passage, because it determines preventive strategies














Stone composition


Additional information


Calcium oxalate (MC type)


Risk factors




  • Hypercalciuria: due to hypercalcemia (e.g., multiple myeloma, sarcoidosis) or idiopathic renal hypercalciuria



  • Hyperoxaluria




    • High oxalate food intake



    • Increased gastrointestinal (GI) absorption of oxalate: dietary calcium combines with oxalates and forms a compound that cannot be absorbed from GI tract into the circulation. In fat malabsorption, unabsorbed fat binds with calcium leaving oxalates to be readily absorbed into circulation and then to urine



  • Hypocitraturia: citrate prevents calcium-oxalate stone formation


Prevention: the following dietary modifications are recommended to prevent calcium stones formation:




  • Increase fluid intake



  • Decrease sodium, oxalate, and protein intake


! It is not recommended to decrease dietary calcium



MRS

Decrease SOP intake
























Stone composition


Additional information


Calcium phosphate


Found in primary hyperparathyroidism, as parathyroid hormone promotes phosphaturia


Magnesium-aluminum phosphate stone (aka struvite stone or staghorn calculus)


This is the only stone that forms in an alkaline environment. Urease-producing bacterial infection predisposes to formation of this type of stones



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Source: Common clinical problems. In: Gunderman R. Essential radiology. Clinical presentation, pathophysiology, imaging. 3rd ed. Thieme; 2014.


Rx: do percutaneous nephrolithotomy. These stones are frequently colonized and can predispose to recurrent infection, unless removed


Uric acid stones


Forms in low urine pH
This is the only stone that is usually radiolucent. It cannot be seen on plain X-ray but can be seen by ultrasound or CT scan
Risk factors: hyperuricosuria due to gout, hematologic malignancies, etc.
Rx: urinary alkalization (with either oral potassium citrate or potassium bicarbonate) can dissolve the stone. Uric acid stones are most readily dissolvable. Allopurinol is indicated for recurrent uric acid stone


Cystine stones


Hereditary disorder of failure to reabsorb cystine amino acid from renal tubules, resulting in cystinuria. Cystine stones are only faintly radiodense
Lab findings: Urine nitroprusside test will be positive and UA will show hexagonal crystals



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Source: Urea synthesis disorders. In: Riede U, Werner M. Color atlas of pathology: Pathologic principles, associated diseases, sequela. 1st ed. Thieme; 2004.


Rx: alkalization of urine with potassium citrate. For stones > 1 cm, surgical extraction is done. It is not amenable to shock wave lithotripsy



MRS

Proteus MUSt kill urea. Proteus, Morganella, Ureaplasma, SerraTia, Klebsiella, etc. produce urease (which breaks down urea)



In a nutshell

Types of hematuria

















Early/initial hematuria


Indicates urethral source, as proximal blood is flushed out by urine


Terminal hematuria


From prostate, bladder neck, or trigone area




  • Bladder compression of this area occurs at the end of urination


Continuous or total hematuria


Bleeding at the level of mid-bladder or higher



Clinical Case Scenarios

A 25-year-old female presents with urinary frequency, urgency, dysuria, and hesitancy for the last few days. Exam reveals suprapubic pain and mucopurulent discharge out of urethra. She has hx of multiple sexual partners. UA is leukocyte esterase positive but nitrites negative.


1. What is the likely Dx?


2. What is the treatment?


A 42-year-old male presents with few weeks hx of urinary frequency, urgency, dysuria, and dribbling of urine. For the last few days he also started noticing painful, tender, and swollen testes. Exam reveals tender testes and prostate.


3. What is the likely dx?


4. What is the MCC?


5. What is the treatment and duration?


6. Patient has bile salt deficiency due to ileitis in Crohn’s disease. What type of urinary stone would you expect?


7. A 67-year-old male has few years hx of intermittent bloody urine, urinary frequency, urgency, dysuria, and dribbling of urine. He has no hx of fevers, chills, but has had significant unintentional weight loss. UA shows multiple RBCs and only few WBCs. What is the likely Dx?


8. A 45-year-old male is diagnosed with severe acute transverse myelitis and neurogenic bladder. What is an effective way to reduce risk of UTI in patients with neurogenic bladder?


A patient has ureteral colic. Urine pH is alkaline (pH> 5.4).


9. What two diagnoses should come to your mind?


10. By looking at basic metabolic profile, would you be able to differentiate in between them? A patient has recurrent calcium oxalate stones with no obvious risk factors.


11. What is the NSIDx?


12. If urinary Ca2+ excretion is high and serum Ca2+ is normal, then what is the likely dx?


13. What adjunctive treatment would you give to prevent stone formation?


14. If both urinary Ca2+ and serum Ca2+ are high, what is the likely Dx?


A 50-year-old male presents with few months hx of bloody urine, urinary frequency, urgency, dysuria, difficulty urination, and dribbling of urine. He has no hx of fevers, chills or weight loss. UA shows multiple RBCs and only few WBCs. Prostate exam is unremarkable.


15. What is the NSIDx?


16. If that testing is unremarkable, what is the NSIDx?



6.3 Acute Renal Failure/Acute Kidney Injury



Classification

















Prerenal acute kidney injury (AKI)


Due to renal hypoperfusion


Renal AKI


Due to intrinsic renal disease (e.g., acute tubular necrosis, glomerulopathies)


Postrenal AKI


Due to obstruction



General presentation



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aSevere cases might end up needing emergent dialysis (please see dialysis section for indication).


Best initial test: serum creatinine and blood urea nitrogen (BUN). Creatinine is the most sensitive indicator of renal failure and is used to calculate glomerular filtration rate (GFR). The following properties make creatinine one of the best indicators of renal function:




  • It is usually produced (by breakdown of creatine in muscles) and excreted (by kidneys) in constant amounts and in a highly predictable fashion.



  • It is not reabsorbed and very little is secreted into the renal tubules.



Management



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aIf patient cannot provide good history (e.g., confused patient), first step is to rule out urinary retention by doing a simple bedside test, i.e., bladder scan.


bBladder outlet obstruction is a common reason for acute renal failure in old patients. Causes include urethral stricture, prostate cancer, benign prostatic hypertrophy, cervical cancer, retroperitoneal fibrosis, stone in bladder-neck, atonic bladder, etc.


cFractional excretion of sodium (FENa). In addition to serum sodium and creatinine, we need urine sodium and urine creatinine to calculate this ratio, but no need to remember the formula of FENa as it will be given in exam. A hypoperfused kidney will try to conserve Na by increasing reabsorption of Na+.



7 Caution: Do not rely on FENa when patients are on diuretics or have preexisting tubular disease. In patients on diuresis, use FEUrea instead. Urea is also an osmolyte like Na, but it is not affected by diuretics.

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Dec 11, 2021 | Posted by in NEPHROLOGY | Comments Off on 6. Nephrology
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