eMedicine Specialties > Nephrology > Acid-Base, Fluid, and Electrolyte Disorders

Hyporeninemic Hypoaldosteronism: Differential Diagnoses & Workup

Author: James H Sondheimer, MD, Director of Hemodialysis Unit, Harper Hospital; Associate Professor, Department of Internal Medicine, Division of Nephrology, Wayne State University School of Medicine
Contributor Information and Disclosures

Updated: Oct 7, 2009

Differential Diagnoses

Addison Disease
Metabolic Acidosis

Other Problems to Be Considered

Pseudohyperkalemia

Workup

Laboratory Studies

• The hallmark of diagnosis is the finding of hyperkalemia in the setting of mild-to-moderate chronic kidney disease.
  • First, exclude pseudohyperkalemia, which is seen with difficult venipunctures and in thrombocytosis. Serum is prepared by allowing whole blood to clot in a red top tube. In cases of thrombocytosis, enough potassium is released in vitro by the platelets to materially affect the serum potassium. Plasma, on the other hand, is prepared in a manner to prevent clotting in vitro, so the platelets largely remain intact and, therefore, do not release their cytosolic potassium.
    
    Repeat serum potassium to confirm, with a better venipuncture, if possible.
    
    Obtain a complete blood count (CBC) with platelet count to screen for hyperkalemia caused by thrombocytosis or severe leukocytosis. The measurement of plasma potassium (P_K) can help to confirm the diagnosis of pseudohyperkalemia, if suspected.
  • If adrenal insufficiency is at all suspected, a random cortisol level should be obtained as a screening test. However, a Cortrosyn stimulation test is preferred because it is more sensitive and specific and does not add greatly to the cost and complexity of the workup.
• If the potassium is 6.0 mEq/L or higher, examine the patient with a 12-lead ECG for signs of hyperkalemia. If these signs are found, institute emergent treatment.
• Acidosis generally is mild, with serum bicarbonate levels in the range of 18-22 mEq/L. The bicarbonate level is useful to guide therapy, as discussed in Treatment.
• Because unusual accumulation of unmeasured anions (either of endogenous or exogenous origin) does not occur, the anion gap generally is in the reference range (varies by laboratory). However, some patients in whom the diagnosis of type IV RTA is considered have sufficiently advanced CKD to accumulate endogenous metabolic acids (such as phosphate and urate), leading to a mild elevation of the anion gap.
• Urinary electrolytes
  • This test is useful in a corroborative role. In a healthy patient, high potassium intake is followed by a high urinary potassium excretion rate; in the presence of hyperkalemia, low urinary K is prima facie evidence of inadequate renal potassium excretion. The urinary anion gap is determined by adding sodium and potassium and by subtracting chloride from the sum ([Na + K] – Cl). This value is usually negative, reflecting the unmeasured cation NH ^{₄ +}. However, in impaired ammoniagenesis, as observed in type IV RTA, positive values of 40 or more may be observed. This test has meaning only with adequate distal sodium delivery (ie, U_Na >20 mEq/L) and in the absence of unmeasured anions, such as ketone bodies and lactate.
  • The transtubular potassium gradient (TTKG) is a further refinement of the random urine potassium measurement. Most tubular potassium excretion takes places in the CCT. At that point, urine is usually iso-osmotic to serum.
    • Downstream from the CCT, under the influence of antidiuretic hormone (ADH), the urine becomes concentrated and potassium is neither reabsorbed nor secreted; therefore, the ratio of urinary osmolality (U _Osm ) and plasma osmolality (P _Osm ) is used to estimate the degree of urinary concentration that is relative to the end of the CCT. The urine potassium divided by this ratio is an estimate of the tubular U _K at the end of the CCT. Thus, U _K /(U _{O sm} /P _{O sm} ) is a crude estimate of U _K at that tubular site.
    • The ratio of the estimated tubular U _K to the P_K is known as the TTKG. Thus, TTKG = [U _K /(U _{O sm} /P _{O sm} )]/P _K . Under normal conditions in a healthy person, the TTKG is 8-9. With potassium loading and appropriate aldosterone release and action, it rises to over 11. A value of less than 5 in the setting of hyperkalemia usually means an aldosterone lack, either in its release or in its tubular effect. This interpretation of the TTKG ratio assumes concentrated urine (U _Osm >P _Osm ) and a U_Na level of greater than 25, indicating adequate distal sodium delivery.
  • Note here that if sodium is avidly resorbed more proximally, then inadequate sodium may be delivered to the aldosterone-mediated Na-K exchange site, leading to hyperkalemia, despite the presence of normal or high levels of aldosterone. This situation may be seen in severe congestive heart failure (CHF) or liver failure.
• Measurement of renin and aldosterone has been excluded from routine studies for the following reasons:
  • These levels must be determined under standardized conditions of position and volume status.
  • The tests are costly and usually have a longer turnaround time than routine studies do.
  • The results generally are not useful in guiding therapy; therefore, their use is limited to clinical research studies or to situations in which other endocrinopathies are being considered. In cases of clinical uncertainty, these studies certainly should be obtained.
    • If it is desired to confirm the lack of renin and aldosterone, diurese the patient to achieve mild volume depletion, and then obtain a morning standing blood sample to maximally stimulate the renin-aldosterone axis.
• If the patient is newly presenting, then order a complete workup for the underlying renal disease. Serologic studies for SLE, hepatitis, and HIV, as indicated, may be necessary in many patients. See Chronic Renal Failure
• Urine pH, performed with a pH meter, confirms that the patient can produce acidified urine (pH <5.3). This distinguishes type IV RTA from type I (ie, distal) RTA.

Imaging Studies

• For new patients with CKD, obtain an ultrasound to establish kidney size and to screen for obstruction.

Procedures

• In newly presenting patients with proteinuria, hematuria, or early stage CKD, a renal biopsy may be necessary for definitive diagnosis of the underlying renal disease.

• Search for CME/CE on This Topic »

• Hyperkalemia (Pediatrics: Cardiac Disease and Critical Care Medicine)