Renal involvement in paroxysmal nocturnal haemoglobinuria: a brief review of the literature

Abstract

SUMMARY INTRODUCTION: Paroxysmal Nocturnal Haemoglobinuria (PNH) is an acquired genetic disorder characterized by complement-mediated haemolysis, thrombosis and variable cytopenias. Renal involvement may occur and causes significant morbidity to these patients. OBJECTIVE: To review the literature about pathophysiology and provide recommendations on diagnosis and management of renal involvement in PNH. METHODS: Online research in the Medline database with compilation of the most relevant 26 studies found. RESULTS: PNH may present with acute kidney injury caused by massive haemolysis, which is usually very severe. In the chronic setting, PNH may develop insidious decline in renal function caused by tubular deposits of hemosiderin, renal micro-infarcts and interstitial fibrosis. Although hematopoietic stem cell transplantation remains the only curative treatment for PNH, the drug Eculizumab, a humanized anti-C5 monoclonal antibody is capable of improving renal function, among other outcomes, by inhibiting C5 cleavage with the subsequent inhibition of the terminal complement pathway which would ultimately give rise to the assembly of the membrane attack complex. CONCLUSION: There is a lack of information in literature regarding renal involvement in PNH, albeit it is possible to state that the pathophysiological mechanisms of acute and chronic impairment differ. Despite not being a curative therapy, Eculizumab is able to ease kidney lesions in these patients.

Pediatric Paroxysmal Nocturnal Hemoglobinuria Presenting as Acute Kidney Injury

“…12 Multiple theories regarding the development of AKI in patients with PNH have been proposed, but the most prominent theory focuses on the increased levels of free circulating hemoglobin. [12][13][14][15] Typically, free hemoglobin is bound with haptoglobin to create a hemoglobin-haptoglobin complex that gets degraded in the liver or spleen. When there is recurrent intravascular hemolysis, native haptoglobin stores are depleted, allowing free hemoglobin to dimerize and be broken down by the renal tubular cells instead.…”

“…Multiple theories regarding the development of AKI in patients with PNH have been proposed, but the most prominent theory focuses on the increased levels of free circulating hemoglobin 12–15. Typically, free hemoglobin is bound with haptoglobin to create a hemoglobin-haptoglobin complex that gets degraded in the liver or spleen.…”

Complement Inhibition Therapy and Dialytic Strategies in Paroxysmal Nocturnal Hemoglobinuria: The Nephrologist’s Opinion

“…The link between PNH and the kidney has been increasingly investigated and validated through its modern history [80,81]. One of the main features of PNH is intravascular hemolysis, which can be chronic, resulting in iron deposition in the kidneys [82], often accompanied by severe hemolytic episodes causing massive hemoglobinuria and AKI, probably from (ATN) development [83] (Table 1).…”

Laboratory involvement in the diagnosis and monitoring of paroxysmal nocturnal hemoglobinuria: a case report

“…El único tratamiento curativo de enfermedad es el trasplante de células madres hematopoyéticas. Está indicado como tratamiento de primera línea solo en pacientes que asocien una insuficiencia medular grave debido a su elevada morbimortalidad (8).…”