The kidneys in paroxysmal nocturnal hemoglobinuria

Abstract

Long-term study of 21 PNH patients revealed an unexpectedly high incidence of functional and anatomic renal abnormalities. Most patients demonstrated varying degrees of hematuria and proteinuria distinct from hemoglobinuria. Evaluation of renal function revealed hyposthenuria, abnormal tubular function, and declining creatinine clearance. Radiologically these patients had enlarged kidneys, cortical infarcts, cortical thinning, and papillary necrosis which were confirmed by autopsy studies. Hypertension developed in eight patients. Urinary tract infection was uncommon. The renal findings bear striking similarity to those of sickle cell anemia. Contrary to the usual opinion, out studies clearly showed evidence of widespread renal pathology in PNH most likely due to repeated microvascular thrombosis similar to the venous thrombosis involving other organs in this disorder.

Effect of eculizumab on haemolysis‐associated nitric oxide depletion, dyspnoea, and measures of pulmonary hypertension in patients with paroxysmal nocturnal haemoglobinuria

“…Intravascular haemolysis is associated with many common signs and symptoms in PNH and other haemolytic syndromes including thrombosis, fatigue, impaired quality of life, haemoglobinuria, dyspnoea, dysphagia, abdominal pain, anaemia, and erectile dysfunction (Hillmen et al, 2004Hill et al, 2005c;Rother et al, 2005;Schubert et al, 2008). These signs and symptoms in PNH, and in patients with other haemolytic syndromes, are tied to catastrophic outcomes, including acute renal failure, chronic kidney disease, stroke/ transient ischaemic attack, ischaemic bowel, hepatic failure, and deep vein thrombosis (Clark et al, 1981;Vellenga et al, 1982;Doukas et al, 1984;Hillmen et al, 1995Hillmen et al, , 2007 Adams Hill et al, 2005a,c). Many of these symptoms have been under-recognised as significant contributors to morbidity and mortality in patients with PNH and other haemolytic diseases.…”

Management of Paroxysmal Nocturnal Haemoglobinuria: a personal view

“…Although it has been reported that some measure of renal failure is not uncommon in PNH, fortunately this is mostly of low grade (Clark et al, 1981) and not rate-limiting for the production of EPO. Indeed, in PNH the endogenous EPO levels tend to be very high (higher than in other chronic anaemias: (McMullin et al, 1996): thus, in general there is no clear rationale for the use of EPO in PNH.…”

Long‐term safety and efficacy of sustained eculizumab treatment in patients with paroxysmal nocturnal haemoglobinuria

“…Compared with the general population, patients with PNH have a 62-fold higher risk of a TE (McKeage, 2011) and a six-fold greater risk of chronic kidney disease (CKD) . TEs have been reported to account for up to 67% of PNH-related deaths (Hillmen et al, 2007), while CKD has been reported to account for 8-18% of disease-related mortality (Clark et al, 1981;Nishimura et al, 2004).…”