39.2 Nephrology: Acute Kidney Injury, Chronic Kidney Disease and Dialysis, Sodium and Potassium Disorders, Acid-Base Analysis, Urinary Tract Infections, Glomerular Diseases (Nephritic and Nephrotic), Kidney Stones, Renal Tumors and Sexually Transmitted Infections

Why this area matters

Chronic kidney disease is a major and growing cause of illness and death in the Philippines, and kidney failure (mostly from diabetes and hypertension, and chronic glomerulonephritis) is one of the most common reasons for hemodialysis, which PhilHealth helps to fund. AKI from leptospirosis, dengue, sepsis and dehydration is frequent. Sexually transmitted infections are rising among young adults. The PLE asks you to classify AKI, read electrolytes and ABGs, and choose first-line therapy.

Acute Kidney Injury (AKI) & Dialysis Indications

Acute kidney injury is an abrupt decline in renal filtration capacity occurring over hours to days, diagnosed and staged by the Kidney Disease: Improving Global Outcomes (KDIGO) criteria:

• Stage 1: Serum creatinine increase $\ge 0.3\text{ mg/dL}$ ($\ge 26.5\text{ }\mu\text{mol/L}$) within 48 hours, or $1.5\text{ to }1.9$ times baseline within 7 days; or urine output $< 0.5\text{ mL/kg/hour}$ for 6 to 12 hours.
• Stage 2: Serum creatinine $2.0\text{ to }2.9$ times baseline; or urine output $< 0.5\text{ mL/kg/hour}$ for $\ge 12\text{ hours}$.
• Stage 3: Serum creatinine $\ge 3.0$ times baseline, or increase $\ge 4.0\text{ mg/dL}$ ($\ge 353.6\text{ }\mu\text{mol/L}$), or initiation of renal replacement therapy; or urine output $< 0.3\text{ mL/kg/hour}$ for $\ge 24\text{ hours}$, or anuria for $\ge 12\text{ hours}$.

Etiologic Differentiation of AKI

Emergent Indications for Dialysis: The "AEIOU" Mnemonic

1. A — Acidosis: Severe metabolic acidosis refractory to medical therapy ($\text{pH} < 7.1-7.2$).
2. E — Electrolytes: Severe, refractory hyperkalemia ($\text{K}^+ > 6.5\text{ mEq/L}$) with ECG abnormalities (peaked T waves, PR prolongation, widened QRS, sine wave) refractory to medical shifting (calcium gluconate, insulin/dextrose, albuterol, loop diuretics).
3. I — Ingestions / Intoxications: Dialyzable toxic substances (mnemonic SLIME: Salicylates, Lithium, Isopropanol, Methanol, Ethylene glycol).
4. O — Overload: Refractory pulmonary edema and volume overload unresponsive to maximal diuretic escalation.
5. U — Uremia: Symptomatic uremic manifestations: uremic encephalopathy (altered mental status, asterixis, seizures), uremic pericarditis (pericardial friction rub, risk of tamponade), or uremic bleeding diathesis (platelet dysfunction due to circulating guanidinosuccinic acid).

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Chronic Kidney Disease (CKD) & Complications

CKD is defined as abnormalities of kidney structure or function persisting for $\ge 3\text{ months}$, with implications for health.

KDIGO Staging by eGFR & Albuminuria

• eGFR Categories (mL/min/1.73 m²):
  • G1: Normal or high ($\ge 90$ with structural kidney damage).
  • G2: Mildly decreased ($60 - 89$).
  • G3a: Mildly to moderately decreased ($45 - 59$).
  • G3b: Moderately to severely decreased ($30 - 44$).
  • G4: Severely decreased ($15 - 29$).
  • G5: Kidney failure ($< 15$ or on chronic dialysis).
• Albuminuria Categories (Urine Albumin-to-Creatinine Ratio, UACR):
  • A1 (Normal to mildly increased): $< 30\text{ mg/g}$ ($< 3\text{ mg/mmol}$).
  • A2 (Moderately increased): $30 - 300\text{ mg/g}$ (formerly microalbuminuria).
  • A3 (Severely increased): $> 300\text{ mg/g}$ (includes nephrotic-range proteinuria $> 2,200\text{ mg/g}$).

Major Complications of Progressive CKD

• Anemia of CKD: Normochromic, normocytic anemia primarily caused by decreased peritubular interstitial synthesis of erythropoietin (EPO). Evaluated when hemoglobin is $< 12.0\text{ g/dL}$ in women or $< 13.0\text{ g/dL}$ in men. Prior to initiating Erythropoiesis-Stimulating Agents (ESAs: epoetin alfa, darbepoetin), iron stores must be replete (transferrin saturation $\ge 20\%$ and serum ferritin $\ge 100-200\text{ ng/mL}$). Target hemoglobin with ESAs is $10.0\text{ to }11.5\text{ g/dL}$; targeting higher levels ($> 13.0\text{ g/dL}$) increases strokes, vascular access thrombosis, and cardiovascular mortality.
• CKD-Mineral and Bone Disorder (CKD-MBD): Declining GFR impairs phosphate excretion (hyperphosphatemia) and diminishes renal 1-alpha-hydroxylase activity, reducing active $1,25\text{-(OH)}_2\text{D}_3$ (calcitriol) synthesis. The resulting hypocalcemia and hyperphosphatemia stimulate parathyroid hyperplasia, triggering severe secondary hyperparathyroidism and high-turnover bone disease (osteitis fibrosa cystica / renal osteodystrophy). Treatment entails dietary phosphate restriction, non-calcium phosphate binders (Sevelamer, Lanthanum), active vitamin D analogues (Calcitriol, Paricalcitol), and calcimimetics (Cinacalcet).

More on kidney failure:

• AKI causes common in the Philippines: leptospirosis (after floods; jaundice with AKI and often non-oliguric hypokalemic renal failure), dengue, sepsis, rhabdomyolysis, contrast, herbal remedies and NSAIDs.
• Acute interstitial nephritis: drugs (penicillins, NSAIDs, PPIs), with fever, rash, eosinophilia and white cell casts. Stop the drug, with steroids for some.
• Slowing CKD progression:
  • BP control (KDIGO suggests systolic below 120 mmHg if tolerated);
  • an ACE inhibitor or ARB at maximum tolerated dose for albuminuria;
  • an SGLT2 inhibitor for most patients with eGFR of 20 or more;
  • finerenone in diabetic kidney disease with albuminuria;
  • glucose control, statins, stopping smoking;
  • avoiding nephrotoxins and adjusting drug doses.
• Renal replacement: prepare for dialysis or transplantation when eGFR falls below about 20 to 30 (an arteriovenous fistula takes months to mature). Kidney transplantation gives the best survival and quality of life.

Sodium and potassium disorders

• Hyponatremia (sodium below 135 mmol/L):
  • check serum osmolality: high (hyperglycemia, mannitol), normal (pseudohyponatremia from lipids or protein) or low (true hypotonic hyponatremia);
  • assess volume status:
    • hypovolemic: GI losses (urine sodium below 20), thiazides and adrenal insufficiency (urine sodium above 20);
    • euvolemic: SIADH, hypothyroidism, secondary adrenal insufficiency, primary polydipsia, beer potomania;
    • hypervolemic: heart failure, cirrhosis and nephrotic syndrome;
  • severe symptoms (seizures, coma): 3% saline 150 mL over 20 minutes, repeated if needed, aiming for a rise of 4 to 6 mmol/L;
  • chronic hyponatremia: correct by no more than 8 to 10 mmol/L in 24 hours (8 in high-risk patients such as those with alcohol use or malnutrition) to prevent osmotic demyelination (dysarthria, quadriparesis).
• Hypernatremia: water loss with poor access to water (elderly, infants, diabetes insipidus). Replace the free water deficit slowly (no more than about 10 to 12 mmol/L a day in chronic cases) to avoid cerebral edema.
• Hyperkalemia:
  • causes: CKD and AKI, ACE inhibitors, ARBs, spironolactone, NSAIDs, trimethoprim, adrenal insufficiency, acidosis, tissue breakdown (rhabdomyolysis, tumor lysis) and pseudohyperkalemia (hemolyzed sample);
  • ECG progression: peaked T waves, PR prolongation and flattened P waves, widened QRS, then a sine wave and VF or asystole;
  • treatment:
    • stabilize the heart: IV calcium gluconate if there are ECG changes;
    • shift potassium into cells: regular insulin 10 units with glucose, nebulized salbutamol, and bicarbonate if acidotic;
    • remove potassium: loop diuretics, potassium binders (sodium zirconium cyclosilicate, patiromer, sodium polystyrene sulfonate) and dialysis.
• Hypokalemia:
  • causes: diarrhea, vomiting, diuretics, hyperaldosteronism, insulin and beta-agonists, hypomagnesemia (correct magnesium first), periodic paralysis (thyrotoxic in Asian men) and renal tubular acidosis;
  • ECG: flat T waves, U waves and arrhythmias;
  • weakness, ileus and rhabdomyolysis;
  • replace orally if possible; IV potassium no faster than about 10 to 20 mmol/hour through a peripheral line.

Acid-base analysis

• Steps:
  1. Look at the pH (acidemia below 7.35, alkalemia above 7.45).
  2. Find the primary disorder (bicarbonate for metabolic, PaCO2 for respiratory).
  3. Check compensation: in metabolic acidosis, expected PaCO2 is 1.5 × HCO3 + 8 (± 2) (Winter formula).
  4. Calculate the anion gap: Na minus (Cl plus HCO3), normal about 8 to 12, corrected for low albumin.
  5. In high anion gap acidosis, compare the change in anion gap with the change in bicarbonate to detect a hidden second disorder.
• High anion gap metabolic acidosis: lactic acidosis, ketoacidosis (diabetic, alcoholic, starvation), renal failure and toxins (methanol, ethylene glycol, salicylates, iron, isoniazid). An osmolal gap suggests toxic alcohols.
• Normal anion gap (hyperchloremic) acidosis: diarrhea, renal tubular acidosis, ureteral diversion and saline infusion.
• Metabolic alkalosis:
  • saline-responsive (urine chloride below 20): vomiting, nasogastric suction, diuretics;
  • saline-resistant: hyperaldosteronism, Cushing syndrome, Bartter and Gitelman syndromes.
• Respiratory acidosis: hypoventilation (COPD, sedatives, neuromuscular weakness). Respiratory alkalosis: anxiety, pain, PE, early salicylate toxicity, sepsis and pregnancy.

Urinary tract infections

• Acute uncomplicated cystitis in non-pregnant women: dysuria, frequency and urgency without fever. Treated with nitrofurantoin for 5 days, fosfomycin once, or TMP-SMX where resistance is low. A urine culture is not routinely needed.
• Acute pyelonephritis:
  • fever, flank pain, costovertebral angle tenderness, often with vomiting;
  • urine culture first;
  • an oral fluoroquinolone for mild cases if resistance is low, or IV ceftriaxone for admitted patients;
  • imaging for failure to improve in 48 to 72 hours, to look for obstruction or abscess.
• Complicated UTI: men, pregnancy, catheters, obstruction, diabetes and immunosuppression. Treated longer and guided by culture.
• Asymptomatic bacteriuria: treat only in pregnancy and before urologic procedures that breach the mucosa. Do not treat elderly or catheterized patients without symptoms.
• Recurrent UTI: behavioral measures, vaginal estrogen after menopause, and prophylaxis.

Glomerular diseases

• Post-streptococcal GN: 1 to 3 weeks after pharyngitis or 3 to 6 weeks after skin infection (impetigo), with cola-colored urine, edema, hypertension, low C3 and a high ASO or anti-DNase B. Usually resolves with supportive care (salt and fluid restriction, diuretics, antihypertensives).
• IgA nephropathy: gross hematuria within 1 to 2 days of a respiratory infection ("synpharyngitic"), normal complement. It is the most common primary GN worldwide.
• Rapidly progressive GN (crescents): anti-GBM disease (Goodpasture: lung hemorrhage), ANCA vasculitis and immune complex GN. Needs urgent biopsy, steroids, cyclophosphamide or rituximab, and plasma exchange for anti-GBM.
• Complications of nephrotic syndrome: venous thrombosis (renal vein thrombosis, especially in membranous nephropathy), infections, hyperlipidemia and AKI.
• Secondary causes to look for in the Philippines: hepatitis B (membranous), hepatitis C, HIV, SLE, diabetes, malaria and drugs.
• Kidney biopsy in adults with nephrotic syndrome or unexplained nephritis.

Kidney stones and renal tumors

• Acute renal colic: NSAIDs for pain, non-contrast CT, alpha-blockers for distal ureteral stones of 5 to 10 mm, and urgent drainage for infection with obstruction (see urology).
• Prevention:
  • fluid intake to make more than 2 to 2.5 L of urine a day;
  • a normal calcium diet (restricting calcium raises oxalate absorption);
  • low sodium and less animal protein;
  • thiazides for hypercalciuria, potassium citrate for hypocitraturia and uric acid stones, and allopurinol for hyperuricosuria.
• Renal tumors:
  • renal cell carcinoma (clear cell, linked to smoking, obesity, VHL): hematuria, flank pain and mass, often found by chance on imaging; paraneoplastic polycythemia, hypercalcemia and hypertension;
  • angiomyolipoma (tuberous sclerosis);
  • Wilms tumor in children;
  • urothelial cancer of the renal pelvis;
  • treated by nephrectomy (see surgery).

Sexually transmitted infections

• Urethral discharge in men: gonorrhea and chlamydia. Treat gonorrhea with ceftriaxone 500 mg IM once, adding doxycycline 100 mg twice daily for 7 days if chlamydia is not excluded.
• Vaginal discharge:
  • bacterial vaginosis: fishy odor, clue cells, pH above 4.5, treated with metronidazole;
  • trichomoniasis: frothy discharge, strawberry cervix, treated with metronidazole for the patient and partner;
  • candidiasis: thick white discharge with itching, normal pH, treated with azoles.
• Genital ulcers:
  • primary syphilis: a painless indurated chancre with painless nodes;
  • herpes simplex: painful multiple vesicles and ulcers, treated with acyclovir or valacyclovir;
  • chancroid (Haemophilus ducreyi): a painful ulcer with suppurative nodes;
  • LGV: transient ulcer then painful matted nodes.
• Syphilis:
  • diagnosed with a non-treponemal test (RPR, VDRL) and a treponemal test (TPHA, TPPA);
  • primary, secondary and early latent syphilis: benzathine penicillin G 2.4 million units IM once;
  • late latent syphilis: 3 weekly doses;
  • neurosyphilis: IV aqueous penicillin;
  • the Jarisch-Herxheimer reaction (fever after the first dose) is self-limited;
  • screen every pregnant woman to prevent congenital syphilis.
• Syndromic management treats the likely causes of a syndrome at the first visit where laboratory tests are unavailable. Partner notification, condoms, HIV testing, HPV and hepatitis B vaccination, and HIV PrEP for high-risk people are part of care.