This patient has adult PKD. In PKD, thin-walled spherical cysts develop in the cortex and medulla of both kidneys from birth. The cysts range from millimeters to centimeters in diameter and are usually visible on ultrasonography or computed tomography (CT) by 25 years of age. Renal ultrasound is the diagnostic method of choice for screening individuals at risk. Sensitivity is >85% in those from 20 to 30 years of age. Although proteinuria is common in PKD, it rarely exceeds 2 g/day. Immunoglobulin A nephropathy may present with hematuria but is usually associated with erythrocyte casts and glomerulonephritis. Complement levels are normal in PKD and have no role in the diagnosis of this disorder. Renal biopsy is not necessary for the diagnosis.

An epigastric bruit with both systolic and diastolic components is suggestive of renal artery stenosis, which if hemodynamically significant may manifest as renovascular hypertension. This disorder may present as refractory (resistant) hypertension. Abrupt onset of hypertension as well as onset prior to age 30 years or after age 55 years is suggestive of renovascular hypertension. Conversely, gradual onset of hypertension during middle age is typical of essential or primary hypertension.

Acute lowering of BP in this instance has not been shown to be of benefit, and there may be risks attributable to
hypotension and hypoperfusion. There are no particular features of pheochromocytoma to warrant measurement of catecholamines and metanephrines. In this case, the cause of the elevated BP is due to stopping medications, and a change in medications is not indicated.

Prior to imaging, it is important to establish whether the mildly elevated aldosterone may be secondary, particularly as a result of dietary salt restriction combined with a diuretic. Although measurement of renin and aldosterone in the blood may be a useful screening test, elevated aldosterone in a 24-hour urine sample during a time of salt loading provides strong evidence for primary aldosteronism. Adrenal vein sampling at this point would present risk and should not be considered prior to demonstrating an elevated and inappropriate aldosterone level.

In this case, the mildly elevated catecholamines may be due to a rebound effect from stopping clonidine; given her history, poor adherence to medications should be strongly suspected. Another possible reason for the elevated catecholamines is a false-positive test due to analytical interference from labetalol. Regardless, pheochromocytoma is not strongly suggested from the above information, and imaging is not warranted prior to biochemical confirmation. Repeat testing for catecholamines as well as metanephrines is in order; consider a clonidine suppression test only if these results are equivocal.

The hyponatremia and normal renal function (normal BUN and serum creatinine) in conjunction with a low serum uric acid level all suggest SIADH. SIADH is also associated with low uric acid levels. The long history of cigarette smoking and cough suggest the possibility of a lung cancer, well known to be associated with SIADH. No evidence of congestive heart failure or cirrhosis with ascites is described on the physical examination. Although the values for sodium, chloride, and potassium concentration are consistent with adrenal insufficiency, one would expect hyponatremia of this magnitude due to adrenal insufficiency to have clinical and biochemical evidence of extracellular fluid (ECF) volume contraction—that is, a higher BUN, possibly a higher serum creatinine level (depending on the patient’s muscle mass), and a higher serum uric acid level.

This patient has obvious physical findings of ECF volume contraction (orthostatic hypotension and diminished skin turgor). The proper treatment is to administer ECF (i.e., normal saline). Restriction of salt and water is obviously inappropriate for a patient who requires volume expansion. Although hyponatremic, the restriction of free water would only aggravate the hemodynamic abnormalities present. Consideration of demeclocycline should be reserved for patients with evidence of chronic SIADH, a condition that cannot be diagnosed in the setting of obvious ECF volume contraction.

The approach to all acid-base questions should involve the following steps:

1. Are the data internally consistent?

Predicted [H⁺] (nEq/L) = 24 × PCO₂/[]

= 24 × 28/14 = 48 nEq/L.

The pH corresponding to this is ˜7.32, which is very close to the measured pH. Thus, the data are internally consistent.

2. Is the primary disturbance acidosis or alkalosis?

The pH is <7.35; therefore, the patient is acidemic, and the primary disturbance is an acidosis.

3. Is the primary disturbance metabolic or respiratory?

is 14 mEq/L, which is consistent with a metabolic acidosis.

PCO₂ is 28, which is consistent with a respiratory alkalosis. We therefore conclude that respiratory response is likely compensatory and that the primary disturbance is a metabolic acidosis.

4. Is the compensation adequate?

For metabolic acidosis, use the Winter formula to estimate the appropriate PCO₂:

Predicted PCO₂=1.5 · [] + 8 (±2) =1.5 × 14 + 8 = 29.

This is within 2 of the measured PCO₂, so the respiratory compensation is adequate.

5. What is the anion gap (AG)?

The AG is calculated as Na⁺ – (Cl^– + ) = 140 – 118 = 22. The “normal” AG may vary based on the clinical laboratory, but a typical AG is ˜12. Therefore, there is a wide AG metabolic acidosis, which prompts the clinician to consider a different set of diagnoses. Further testing reveals that lactic acidosis is present. Although trace ketones
are present, the glucose is only mildly elevated, and diabetic ketoacidosis is less likely given the more impressive elevation of serum lactate. The patient also has renal insufficiency, which would be a risk factor for the development of lactic acidosis during treatment with metformin. Isopropanol ingestion often produces a ketosis but would not cause an elevated AG. Ethylene glycol ingestion could produce a similar scenario (including the presence of lactic acidosis). However, it is also associated with an elevated osmolar gap and the presence of urinary calcium oxalate monohydrate crystals. Detection of lactic acidosis should prompt the clinician to determine the cause such as tissue hypoperfusion, medications (e.g., metformin, linezolid, stavudine, and didanosine), or toxins (methanol, ethylene glycol, or salicylate). This case is not consistent with an RTA because of the presence of a wide AG.

6. If there is an AG, calculate the ΔAG.

The AG in this case was 22 (normal AG = 12 but may vary by the clinical laboratory), or a ΔAG of 10. If we assume that the ΔAG provides an estimate of the acid load and that 1 mEq/L of acid reduces [] by 1 mEq/L, then this can be added back to the actual [] (14 mEq/L) to estimate the starting concentration of []. In this case, the [] is estimated to be 24 mEq/L before the acidosis occurred.

The approach to all acid-base questions should involve the following steps:

1. Are the data internally consistent?

2. Is the primary disturbance acidosis or alkalosis?

3. Is the primary disturbance metabolic or respiratory?

4. Is the compensation adequate?

5. What is AG?

6. If there is an AG, calculate the ΔAG.

A breakdown of this case is as follows:

1. The data are internally consistent (calculated H⁺ = 32, corresponding to pH ˜7.48).

2. Alkalosis.

3. Respiratory alkalosis. There is a metabolic acidosis, which could be compensatory.

4. Compensation is adequate, assuming the process is chronic.

Using the formula for chronic respiratory alkalosis: ↓Δ[] = 5 × ΔPCO₂/10, we expect [] to decrease by 12, which matches the observed change exactly.

5. AG is normal (10).

6. Because the AG is normal, ΔAG cannot be calculated.

Further discussion: If assessment of the [] were performed without an AG, it might be concluded that treatment with oral supplementation would be appropriate. This would lead to further renal wasting, which would obligate an equal loss of cations (e.g., K⁺, Mg²⁺, Ca²⁺) to maintain electroneutrality, further exacerbating the hypokalemia and hypomagnesemia. Although supplementation with oral potassium or magnesium may be warranted, it does not address the underlying problem. In this case, the respiratory set rate was decreased (gradually over a period of weeks), and , potassium, and magnesium supplementation were gradually tapered. The urinary AG is positive in this case due to renal loss to compensate for the respiratory alkalosis, but this does not diagnose an RTA, as the primary process is not an acidosis. The very low creatinine provides a clue to the low muscle mass of this patient and may suggest that her metabolic demand and thus the need for respiratory excretion of CO₂ may not be as high as a normal patient.

The approach to all acid-base questions should involve the following steps:

1. Are the data internally consistent?

2. Is the primary disturbance acidosis or alkalosis?

3. Is the primary disturbance metabolic or respiratory?

4. Is the compensation adequate?

5. What is AG?

6. If there is an AG, calculate the ΔAG.

A breakdown of this case is as follows:

1. Data are internally consistent.

2. Acidosis. The pH is near normal, although both and PCO₂ are clearly abnormal. The approach to evaluating acidosis is chosen because it is generally simpler and more commonly encountered than for an alkalosis.