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.

Long‐term effect of the complement inhibitor eculizumab on kidney function in patients with paroxysmal nocturnal hemoglobinuria

“…Because of the recognized high incidence (65%) of renal dysfunction or damage at baseline in patients from the TRIUMPH study [27] and the serious and life‐threatening nature of poor renal function in patients with PNH [12], analyses were performed to assess the overall effect of eculizumab treatment on renal function. Eculizumab treatment was significantly more likely to improve CKD stage than placebo treatment through 6 months.…”

“…Clark et al [12] previously reported that 32% (6/19) of patients with PNH had creatinine clearance of <60 ml/min/1.73 m 2 (CKD Stages 3–5), indicating kidney damage. The exact mechanisms responsible for kidney damage in patients with PNH are unclear, but a substantial number of investigations implicate chronic hemolysis leading to hemosiderin accumulation, inflammation, and renal scarring.…”

“…Magnetic resonance imaging (MRI) studies reproducibly show that virtually all patients with PNH are observed to have renal cortical areas of low signal intensity including patients with PNH who have lower levels of hemolysis indicated by no hemoglobinuria for more than 8 years, aplastic anemia, myelodysplastic syndrome (MDS) or chronic myelomonocytic leukemia (CMML), or with smaller PNH clones [7, 10, 16, 35]. Cortical abnormalities detected by intravenous pyelogram have been noted in patients with lower levels of hemolysis as represented by the absence of overt hemoglobinuria [12]. Autopsy or biopsy findings typically showheavy hemosiderin accumulation in the proximal tubules, hemoglobin tubular casts, signs of chronic interstitial nephritis, and fibrosis [12].…”

“…Cortical abnormalities detected by intravenous pyelogram have been noted in patients with lower levels of hemolysis as represented by the absence of overt hemoglobinuria [12]. Autopsy or biopsy findings typically showheavy hemosiderin accumulation in the proximal tubules, hemoglobin tubular casts, signs of chronic interstitial nephritis, and fibrosis [12]. When examined, functional tubular defects are commonly found with impaired ability to concentrate urine, renal tubular acidosis, decreased reabsorption of phosphate, glucosuria with normal blood sugar, and aminoaciduria [12, 36].…”

“…Kidney failure contributes to 8%–18% of PNH‐related deaths [6]. Virtually all patients with PNH have evidence of kidney damage by biopsy or imaging techniques or at postmortem examination [7–16]. Previous reports showed that repetitive exposure to cell‐free hemoglobin causes renal hemosiderin accumulation, tubulointerstitial inflammation, and kidney damage [17].…”