Chronic renal failure differential diagnosis

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Aarti Narayan, M.B.B.S [2]Feham Tariq, MD [3]

Overview

Differentiating chronic renal failure from acute renal failure and from the condition of having an increased BUN with a normal GFR are the most important diagnostic step in evaluating a patient with raised serum creatinine levels, as these conditions can be treated with therapy specific to the underlying etiology.

Distinguishing chronic renal failure from acute renal failure

• Elevated creatinine levels from recent weeks or months suggest that the current disease process is more acute and hence reversible. On the other hand, long standing elevated serum values suggests a chronic disease process.
• Even if the elevated serum creatinine levels are chronic, there is a possibility of the patient having a superimposed acute process over a chronic condition such as: a urinary tract obstruction, infections, extra cellular fluid volume depletion, or nephrotoxin exposure.
• If the patient's history suggests an array of recent onset symptoms e.g:fever, rash and/or polyarthralgia, it can be safely concluded that the renal insufficiency is a part of an acute process.

Distinguishing chronic renal failure from an increased BUN with normal GFR

• The key differentiating factor between the condition of an increased BUN with a normal GFR and chronic renal failure is a normal glomerular filtration rate (GFR).

Other differentials

Uremia due to chronic renal failure should be differentiated from other diseases causing hypertension and hypokalemia for example:

• Renal artery stenosis
• Cushing's syndrome
• Congenital adrenal hyperplasia (CAH)
  • 17 alpha hydroxylase deficiency
  • 11 beta hydroxylase deficiency
• Liddle's syndrome
• Diuretic use
• Licorice ingestion
• Renin-secreting tumors

Hypertension and Hypokalemia

Plasma renin activity

Normal or High (Plasma Renin/Aldosterone ratio <10

Suppressed (Plasma Renin/Aldosterone ratio >20

*Renin-secreting tumors *Diuretic use *Renovascular hypertension *Coarctation of aorta *Malignant phase hypertension

Urinary aldosterone

Elevated

Normal

Low

Conn's syndrome (Primary aldosteronism)

Profound K+ depletion

• 17 alpha hydroxylase deficiency • 11 beta hydroxylase deficiency • Liddle's syndrome • Licorice ingestion • Deoxycortisone producing tumor

Add Mineralocrticoid antagonist for 8 weeks

BP response

No BP response

• Deoxycorticosterone excess( Tumor, 17 alpha hydroxylase and 11 beta hydroxylase deficiency) • Licorice ingestion •Glucocorticoid resistance

Liddle's syndrome)

Differential Diagnoses	Clinical features											History Findings	Laboratory Findings
	Headache and hypertension	Nausea and vomiting	Palpitations	Shortness of breath	Diminished pulses	Fatigue	Constipation	Visual abnormalities	Pruritis	Polyuria	Ambiguous genitalia
Renin-Secreting tumors	✔ (Due to hypertension)	✔	✔	✔	-	-	-	-	-	-	-	Drug-resistant hypertension Chronic headaches	Normal renal function tests Normal liver function tests Metabolic alkalosis (pH > 7.45) Hypokalemia Plasma renin-aldosterone ratio <10
Coarctation of aorta	✔	✔	✔	✔	✔	✔	-	-	-	-	-	Young patients (neonates) may have history of: Failure to thrive Poor feeding Lethargy Turner's syndrome Familial predisposition Ventricular septal defects Adults may have a history of: Claudication Epistaxis	Bicuspid aortic valves Notching of ribs Metabolic alkalosis (pH > 7.45) Hyperkalemia Plasma renin-aldosterone ratio <10
11-beta hydroxylase deficiency	✔ (Hypertensive crisis due to increased 11-deoxycorticosterone-11-DOC)	✔	✔	-	-	✔	-	-	-	-	✔	Females: Clitoral enlargement Labioscrotal fusion Males: Penile enlargement (If not diagnosed at birth, may present as premature adrenarche, developing body odor with axillary and pubic hair development)	Hypokalemia Increased 11-DOC levels Increased androgens Low urinary aldosterone level
17-alpha hydroxylase deficiency	✔	✔	✔	-	-	-	-	-	-	-	✔	Phenotypically females at birth Lack of pubertal development in females Incompletely developed external genitalia in males	Increased serum mineralocorticoids Decreased androgen levels Hypokalemia Low urinary aldosterone level
Uremia		✔	✔	✔	-	✔	✔	-	✔	-	-	Patients have chronic kidney disease and maybe on dialysis Features of uremic neuropathy: Autonomic features with postural hypotension, Impaired sweating Diarrhea Impotence Paraesthesia Delayed deep tendon reflexes Muscle wasting Encephalopathy	Increased blood urea nitrogen (BUN) and creatinine (Cr) Hyperkalemia Decreased serum vitamin 1,25 dihydroxy vitamin D3 level
Liddle's syndrome	✔	✔	✔	-	-	-	✔	-	-	-	-	Family history of Liddle's syndrome (autosomal dominant inheritance) Nephropathy Arrythmias SCNN1B or SCNN1G gene mutation	Hyporeninemic hypoaldosteronism Hypertension Hypokalemia Enhanced erythrocyte sodium influx  Low urinary aldosterone

Etiology

• Prerenal azotemia
• Catabolic states
• High protein diet
• Gastrointestinal bleeding
• Glucocorticoids
• Tetracycline

References

1.Zeiger Roni F. "Harrison's Textbook of Internal Medicine". McGraw-Hill's Diagnosaurus 2.0.

2.Bargman JM, Skorecki K. "Chapter 280. Chronic Kidney Disease. In: Longo DL, Fauci AS, Kasper DL, Hauser SL, Jameson JL, Loscalzo J, eds. Harrison's Principles of Internal Medicine. 18th ed". New York: McGraw-Hill; 2012.