DKD-related anemia developed earlier and was more severe than non-DKD-related anemia based on more complicated mechanisms, including greater bleeding tendency associated with antiplatelet effect, less O2 sensing due to autonomic neuropathy or renin-angiotensin-aldosterone system inhibitor use, inhibitory effect of inflammatory cytokines, urinary loss of erythropoietin (EPO), and poor response to EPO.
These factors include: (1) activation of the renin-angiotensin-aldosterone system, (2) anemia, (3) hypercalcemia, hyperphosphatemia and increased levels of FGF-23, and (4) uremic toxins.
Heterozygous mutations in the gene encoding renin (REN) cause autosomal dominant tubulointerstitial kidney disease (ADTKD), early-onset anaemia and hyperuricaemia; only four different mutations have been described in the published literature to date.
In multivariate analysis, in the non-extremely elderly group, age (HR 1.027, P < 0.001), body mass index (HR 0.919, P < 0.001), New York Heart Association III or IV (HR 3.626, P < 0.001), preserved ejection fraction (HR 0.553, P < 0.001), anemia (HR 1.941, P < 0.001), β-blockers (HR 0.695, P = 0.028) and renin-angiotensin system inhibitors (HR 0.603, P = 0.001) were independent predictors for all-cause death.
ADKTKD-REN is associated with signs of hyporeninemia: mild hypotension, mild hyperkalemia, anemia in childhood, and hyperuricemia and gout in the teenage years.
A similar clinical syndrome causing the autosomal dominant inheritance of chronic kidney disease, hyperuricemia, and anemia has recently been attributed to mutations in the REN gene encoding renin.
Within the kindred, we found affected individuals over 4 generations who carried the novel REN mutation and were characterized by significant anemia, hyperuricemia, and CKD.
Patients with mutations in the REN gene encoding renin suffer from anemia in childhood, hyperuricemia, mild hyperkalemia, and progressive kidney disease.
A novel REN gene mutation resulted in an alteration in the amino acid sequence of the renin signal sequence and caused childhood anemia, polyuria, and kidney disease.