Clinical Findings & Exam

• Uremia, oliguria/anuria, hematuria

• Prerenal: Tachy, dry mucous membranes, orthostatic HoTN

• Intrarenal: Pulm hemorrhage, palpable purpura → vasculitis + glomerulonephritis, livedo reticularis → atheroembolic dz, limb ischemia → rhabdo

• Postrenal: Flank pain which radiates to groin, suprapubic pain

Diagnostic Workup

Subsequent Workup

• Renal bx: Consider when etiology is unk. 5% complication rate (perirenal hematoma, gross hematuria). Preg: Consider pts <28 w w/ ARF of uncertain etiology when results will change mgmt (Am J Perinatol 2008;25:385)

Treatment

• Correct underlying factors, remove renal toxins, adjust dosing of renally cleared meds. Prevent/treat infxn

• Fluid mgmt: Goal = adequate hydration to reverse preischemic change

• HyperK → polystyrene sulfonate

• Metabolic acidosis → sodium bicarbonate

• RRT (JAMA 2008;299:793)

For ARF refrac to medical mgmt, as evidenced by metabolic acidosis, hyperK, hypervolemia, etc. Mode: IP, intermittent hemodialysis, continuous RRT.

Continuous RRT: Slower solute clearance/min, continuous anticoagulation

Use in Preg:

Symptomatic uremia (changes in mental status, pericarditis, neuropathy)

HyperK not corrected by medical mgmt

Metabolic acidosis

Vol overload

CHRONIC RENAL FAILURE

Definition and Epidemiology (MMR 2007;56:161)

• CKD = abn kidney fxn + progressive decline of estimated GFR for >3 mo

• CRF: Irreversible nephron number reduction

• ESRD: GFR <15 mL/min per 1.73 m² OR need for dialysis &/or xplant

• Prevalence of CKD in US: 16.8% of adults ≥ age 20 (11.1% stages 1–2, 5.8% stages 3–5), & increased prevalence w/ comorbidities such as DM (40.2%), cardiovascular dz (28.2%), & HTN (24.6%)

Etiology

• Glomerular dz: Diabetes, systemic infxn, autoimmune dz

• Vascular dz: HTN, ischemia, atherosclerosis, vasculitis, thromboembolic

• Tubular/interstitial dz: Urinary tract stones, infxn, obst, nephrotoxic meds

Pathophysiology

• Initiating mechanisms: Specific to etiology of CKD

• Progressive mechanisms: Increased renal bld flow/pres → renin–angiotension axis stimulation → nephron hyperfiltration & hypertrophy → glomerular distortion, sclerosis, permanent damage to nephrons → reduction in nephron number

• Failure of renal excretion → accum of toxins (including Cr, urea → uremic syn). Failure of other renal functions → anemia, abn metabolism, fluid/electrolyte imbalance, hormone regulation (glucagon, insulin, Vit D, sex hormones, parathyroid hormone). Progressive inflammation (elevated C reactive prot + acute phase reactants).

Clinical Manifestations

• Edema (from nephrotic syn), fatigue (from anemia), decreased appetite → malnut, inability to perform activities of daily living (uremic syn).

• Preg (CJASN 2011;6:2587): 3 factors correlate w/ ↑ complications: Proteinuria, decreased GFR, HTN

Maternal complications: Gestational HTN, preeclampsia/eclampsia, nephrotic syn, maternal death (higher incid w/ lupus nephropathy)

Fetal complications: Preterm birth, IUGR, IUFD, neonat death

Physical Exam

• Most pts are asymptomatic until mod or sev renal failure develops

• Findings may include periph edema, pericardial friction rub (in presence of uremic syn), sensory neuropathy (evid of end-organ damage)

Diagnostic Workup/Studies

• GFR (mL/min per 1.73 m²) = 1.86 × (PCr) – 1.154 × (age) – 0.203

P_Cr = serum Cr; multiply by 1.21 for AAs or 0.742 for women

• GFR peak = 120 mL/min per 1.73 m² btw age 20 & 30 (lower for women)

• GFR then declines 1 mL/min per 1.73 m² per year

Stages of CKD GFR (mL/min per 1.73 m²)

• Stage 1: ≥90 + kidney damage (proteinuria, abn renal imaging)

• Stage 2: 60–89

• Stage 3: 30–59

• Stage 4: 15–29

• Stage 5: <15

Imaging

• Renal US (preferred modality in Preg)

CKD: Small kidneys bilaterally

Polycystic kidney dz: Cystic, enlarged kidneys

>1 cm discrep in length: Developmental abnormality, arterial insufficiency which affects one kidney more

• Voiding cystogram: To evaluate for reflux nephropathy

• CT, MRI: Avoid IV dye if poss in Preg

• Renal bx: Should be avoided during Preg

• Serial renal fxn measurements (to differentiate acute vs. subacute vs. CKD)

Treatment and Medications

• Potassium sparing meds: ACE inhibitors, ARB, spironolactone, eplerenone, amiloride, triamterene

• Dietary adjustments (decreased salt intake)

• HTN control (Lancet 2005;365:331)

Goal = 130/80 (125/75 in pts w/ diabetes & proteinuria > 1 g/24 h)

Reduce intraglomerular HTN to slow nephron injury progression

• Renal replacement therapy: IP vs. intermittent hemodialysis vs. continuous RRT. Initiate when GFR = 10 mL/min per 1.73 m²

• Preg: 24-h urine total prot in the 1st trimester + HTN control (BB, CCB, hydralazine, clonidine) + Serial USs for fetal growth + antepartum testing: Initiate btw 28 & 32 w. Avoid ACE inhibitors/ARBs.

URINARY TRACT INFECTION (UTI)

Definitions

• Asymptomatic bacteriuria: 10000–100000 CFU/mL in urine culture (Obstet Gynecol 2005;106:1085)

• UTI: ≥100000 CFU/mL in urine culture w/ or w/o sx

• Uncomp: Healthy female w/ nml urinary tract fxn

• Complicated: UTI+ one of the following: Urologic abnormality, urinary calculi, FB (catheter), DM, Preg, spinal cord injury

• Recurrent UTI: 2 Uncomp UTIs in 6 mo or 3 positive cx w/i the preceding 12 mo (Obstet Gynecol Clin North Am 2008;35)

Epidemiology

• 50% will have a UTI in their lifetime; 10% will have a recurrent UTI by age 70

• Asymptomatic bacteriuria in Preg: 20–30× increased risk of pyelo

Etiology

• Escherichia coli = 75–95% (NEJM 2012;366:1028), Proteus (can cause renal calculi). Klebsiella, Enterobacter, Pseudomonas, Staphylococcus saprophyticus (common in young women)

Pathophysiology

• Ascending infxn: Vagina → urethra → bladder

• E. coli: Virulence factors P fimbria, S fimbria, Type 1 fimbria → ↑ uroepithelial/vaginal cell binding, ↑ resistance to host phagocytosis, ↑ resistance to bactericidal activity

Clinical Manifestations and Exam

• Dysuria, increased urgency, increased urinary frequency, suprapubic pain

• Suprapubic tenderness to palpation

• Pyuria, urethral tenderness (seen w/ urethritis)

Diagnostic Workup/Studies

• UA: Leukocyte esterase or nitrites: 75% sensitive, 82% specific (NEJM 2003;349:259); WBC ± RBC; bacteria on gram stain

• Urine culture: ≥100000 CFU/mL

Treatment

PYELONEPHRITIS

Definition

• Infxn of renal pelvicalices/parenchyma from ascending bladder infxn or renal bacteriuria. Clinical syn defined by flank pain, fevers, chills.

Epidemiology

• 23/10000 women ages 15–34 (NEJM 2012;366:1028)

• 1–2% of pregnancies, >50% present in the 2nd trimester (Obstet Gynecol 2005;106:1085)

• Untreated asymptomatic bacteriuria in Preg → 1/4 will develop pyelo

Etiology

• Same as for UTIs (above). Most are E. coli.

Pathophysiology

• Risk factors: Same as for UTI (see UTI section)

• ARDS: IV antibiotic therapy → endotoxin release 24–48 h later → damage to alveolar capillary membranes

• Preg complications

Increased risk of preterm labor if pyelo is not aggressively treated

Pulm insufficiency: Increased risk if temperature >103°F, tachy >110 bpm, gestational age ≥20 w

Clinical Manifestations and Exam

• Chills, fever, flank pain, dysuria, urinary frequency/urgency

• Costovertebral angle tenderness

Diagnostic Workup/Studies

• Urinalysis

• Urine culture w/ susceptibilities

• If no resp to initial therapy, consider bld cx

Treatment and Medications

• Inpt admission is recommended for all women w/ pyelo during Preg (Obstet Gynecol 2005;106:1085)

IV hydration to maintain adequate urine output

Acetaminophen: Hyperthermia can be teratogenic in 1st trimester

IV therapy 24–48 h (avoid fluoroquinolones), follow w/ oral therapy 10–14 d

• Suppression therapy for remainder of Preg: Nitrofurantoin 100 mg PO daily

• Rpt urine culture each trimester

Treatment

NEPHROLITHIASIS

Definition and Epidemiology

• Calcium-based: Calcium oxalate, calcium phosphate (80%) (NEJM 2010;363:954)

• Noncalcium-based: Uric acid, cystine, struvite (may form staghorn calculi)

• 10% of the US pop will have one kidney stone in lifetime (J Urol 2012;188:130)

• Preg: Btw 1/200 to 1/1500 women have symptomatic nephrolithiasis (Cur Op Uro 2010;20:174)

Pathophysiology

• Increased excretion rate or increased water conservation → supersaturation of urine w/ insoluble substances → crystal formation → crystal aggregation into stone(s)

• Stones become symptomatic when entering ureter or occluding uteteropelvic junction

Clinical Manifestations

• Flank pain (episodic, may radiate to abd), nausea, vomiting, hematuria, difficulty finding a comfortable position

Diagnostic Workup/Studies

• CT w/o contrast = imaging modality of choice

• Renal US

• Abdominal radiograph (KUB): Only + if radio-opaque stones

• Preg: Renal US = preferred modality

• Recurrent symptomatic nephrolithiasis: Evaluate poss etiologies

Serum: Calcium, uric acid, electrolytes

Urine: pH, vol, calcium, citrate, oxylate, 24-h urine collection (2 occasions)

Treatment and Medications

• Conservative mgmt: Hydration, pain control (most stones smaller than 0.5 cm pass spontaneously)

• Medical mgmt: Alpha-1 blockers to ↑ motility

• Active intervention req for persistent pain, progressive obst, infxn, solitary kidney obst (J Urol 2012;188:130)

Shock wave lithotripsy: May require multi treatments

Semirigid ureteroscopy: Higher stone free rate after one rx, fewer retreatments needed. Improved success w/ distal ureteral stones.

Percutaneous nephrolithotomy: Most invasive. Use for large stone burden, renal stones.

• Preg: (Cur Op Uro 2010;20:174)

Temporary drainage: Ureteral stent or percutaneous nephrostomy (risk of infxn, bacteriuria, migration/dislodgement)

Definitive rx: Ureteroscopy is preferred

Avoid shock wave lithotripsy in Preg (increased risk of miscarriage, congen malformations, abruption)

FLUIDS AND ELECTROLYTES

Hyperkalemia

• Definition: Serum potassium (K+) >5.5 mEq/L

• Clinical manifestations:

ECG changes (seen when K+ >6 mEq/L): Peaked T waves → 1° heart block → complete heart block → Vfib → asystole

Abdominal pain, myalgias, diarrhea, flaccid paralysis

• Dx:

Rule out pseudohyperkalemia

Urine K+

>30 mEq/L → transcellular shift

<30 mEq/L → impaired renal excretion

• Rx & meds: (J Int Care Med 2005;20:272)

Continuous telemetry

Sodium polystyrene sulfonate (Kayexalate): Cation exchange resin binds K+ → fecal excretion

PO: 30 g diluted in 50 mL of 20% sorbitol, rpt q2h

Rectal: 50 g diluted in 200 mL of 20% sorbitol, rpt q2h

Do not use in pts w/ bowel obst, ileus, bowel ischemia

If ECG changes are present

Calcium gluconate: 10 mL of 10% (1 ampule): IV push over 2 min. Rpt in 5 min.

Calcium chloride: 10 mL of 10% (1 ampule): Use in pts w/ circulatory compromise. 3× more calcium than calcium gluconate → improved cardiac contractility

Insulin/gluc: Give 10 U insulin & 25 g dextrose (1 amp of D₅₀). Hold D₅₀ if bld gluc >250 mg/dL

Albuterol: 10–20 mg of 5 mg/mL nebulized solution

Sodium bicarbonate: Use only in pts w/ sev metabolic acidosis

Dialysis (hemodialysis faster at removing K+ than peritoneal dialysis)

Digitalis tox: Magnesium sulfate 2 g IV bolus. Do NOT use calcium (can potentiate digitalis tox)

Hypokalemia

• Definition: Serum potassium (K+) <3.5 mEq/L

• Clinical manifestations:

Muscle weakness

Nonspecific ECG changes: Prolonged QT interval, flattened inv T waves, U wave (Amp >1 mm)

Digitalis-induced arrhythmia

• Rx:

Treat causes of transcellular K+ shifts

Replace K+: KCl soln w/ 10, 20, 30, or 40 mEq K+. Infuse 20 mEq in 100 mL NS over 1 h

Replace serum magnesium

Hypercalcemia

• Definition: Total serum calcium >11 mg/dL, ionized calcium >3 mmol/L

• Clinical manifestations (seen when ionized calcium >3 mmol/L):

GI: Constip, N/V, ileus, pancreatitis

Renal: Polyuria, nephrocalcinosis

Neuro: Altered mental status, coma

Cardiovascular: HoTN, hypovolemia, decreased QT interval, AV block

• Rx & meds:

Correct hypovolemia: IV hydration w/ isotonic saline

Furosemide: 40–80 mg IV q2h to maintain urine output of 100 mL/h

Calcitonin: To ↓ bone resorption. 4 U/kg q12h SC or IM. Will ↓ serum calcium by 0.5 mmol/L

Hydrocortisone: 200 mg IV daily (divided 2–3 doses). Use w/ calcitonin.

Bisphosphonates: Max resp seen in 4–10 d

Zoledronate 4 mg IV, infuse over 15 min

Pamidronate 90 mg IV, infuse over 2 h

Hypernatremia

• Definition: Serum sodium (Na+) >145 mEq/L

• Clinical manifestations:

Altered mental status

Rhabdo

Absence of thirst vs. intense thirst

Polyuria

Diarrhea

• Diagnostic w/u/studies:

Document fluid intake & urine output

Serum osmolality, urine osmolality, urine electrolytes

• Rx & meds: (NEJM 2000;342:1493)

Stop any continuing causes of HyperNa

Correct serum sodium: Give hypotonic fluid PO or parenterally

Calculate water deficit & daily water loss

Total body water = total body weight × 0.5 in women

Free water deficit = [(serum Na – 140)/140] × TBW

Free water clearance = (V[1 – (UNa + UK)])/PNa

V = urine vol; UNa = urine [Na+]; UK = urine [K+]; PNa = plasma [Na+]

Insensible losses: 10 mL/kg/d

Replace daily water loss, correct water deficit

Chronic HyperNa: ↓ serum Na+ by 10 mmol/d

Avoid correcting too quickly to prevent cerebral edema

Acute HyperNa: ↓ serum Na+ by 1 mmol/L/h

Fluids: Give hypotonic fluids only (0.2% NaCl, 0.45% NaCl)

The more hypotonic the fluid, the lower the rate of infusion

Calculate change in serum Na+ w/ 1 L infusion:

[(infusion Na + infusion K) – serum Na+]/(total body water + 1)

Avoid dextrose solutions (hyperglycemia → osmotic diuresis → worsening HyperNa)

Avoid 0.9% NaCl