Iron in kidneys leads doctors to diagnose man’s PNH: Case report
Red blood cell breakdown provides clues to two conditions
Written by |
Doctors in China diagnosed a man with paroxysmal nocturnal hemoglobinuria (PNH) after a biopsy and specialized MRI, performed to assess kidney problems, yielded clues about ongoing red blood cell breakdown.
The tests identified iron buildup in the man’s kidneys (renal hemosiderosis). The findings raised suspicion of ongoing red blood cell breakdown (hemolysis), a hallmark feature of PNH, prompting further testing that ultimately led to the PNH diagnosis.
The case report, “Renal hemosiderosis in paroxysmal nocturnal hemoglobinuria,” was published in Nephrology Image.
PNH is caused in most cases by mutations in the PIGA gene in blood cell precursors, leading to low or undetectable levels of certain proteins on blood cell surfaces. These proteins normally signal to the immune system that these cells are a healthy part of the body. Without these proteins, however, the immune system can mistakenly attack them.
As a result, blood cells — particularly red blood cells — are prematurely broken down. This leads to a low number of healthy red blood cells (anemia) and the release of hemoglobin (the iron-containing protein in red blood cells that carries oxygen) into the bloodstream. Hemoglobin in the blood is then filtered by the kidneys. When present in excess, it may appear in the urine, a condition called hemoglobinuria that can give the urine a dark color, which is a common PNH symptom. Excess hemoglobin can also be taken up by kidney cells, where its iron is stored as hemosiderin and may accumulate over time. This buildup, known as renal hemosiderosis, can damage kidney tissue and impair kidney function.
MRI, other tests reveal damage
The man in the case report, whom researchers described as “middle-aged,” had had dark-colored urine intermittently for more than 10 years. Laboratory tests showed mild anemia, elevated levels of lactate dehydrogenase (LDH), a marker of blood cell breakdown, and blood and protein in the urine.
A kidney biopsy revealed damage to certain cells of the kidney tubules, tiny structures that filter and process urine, with brown pigment deposits inside them. Special staining confirmed that these deposits were composed of hemosiderin, indicating iron buildup in kidney tissue.
Given these findings, doctors performed an MRI using a specialized quantitative technique to assess iron buildup more broadly. The scans showed reduced signal intensity in the kidney cortex (the outer layer where blood is filtered), consistent with iron accumulation caused by hemoglobin filtration and reabsorption.
Persistently elevated LDH levels indicated ongoing hemolysis, so the doctors performed additional tests to determine the underlying cause. A specialized technique called flow cytometry showed that a portion of the man’s red blood cells lacked key protective surface proteins, suggesting PNH. Genetic analysis confirmed two mutations in the PIGA gene, establishing the diagnosis of PNH with kidney involvement.
Since the man had stable kidney function and only mild anemia, he was treated conservatively with sodium bicarbonate to reduce urine acidity and folic acid to support red blood cell production.
After two years of follow-up, his kidney function remained stable, hemoglobin levels improved, and urine abnormalities resolved.
