Hypoxia inducible factor-prolyl hydroxylase inhibitors in anemic patients with non-dialysis dependent chronic kidney disease: a meta-analysis of randomized clinical trials.

PURPOSE: Anemia persists as a challenge in chronic kidney disease (CKD) patients. Current therapies are the injectable erythropoietin stimulating agents (ESA). Concerns have been raised regarding ESA cardiovascular safety, therefore search for an alternative, convenient and safe therapy is underway. Hypoxia inducible factors-prolyl hydroxylase inhibitors (HIF-PHI) are oral agents with promising results. Numerous small studies reported favorable effects with lack of large, powered studies. METHODS: We conducted a meta-analysis of randomized clinical trials to assess the efficacy and safety of HIF-PHI in non-dialysis-dependent CKD patients. Primary outcome was hemoglobin (Hb) concentration post intervention. Secondary outcomes were all-cause mortality, MACE, and changes in iron metabolism (ferritin, hepcidin). We reported total and serious adverse effects. Data were pooled using a random effect model via RevMan 5.4 software. RESULTS: We identified 7 trials comprising of 8228 patients (mean age 66.5 ± 13.2 years, 42% were females, 53% used iron replacement) with a mean follow-up of 52 weeks. Compared with the standard of care (ESA), HIF-PHI were non-inferior for treatment of anemia, with comparable effect on mortality and major adverse cardiovascular events. HIF-PHI showed no major safety concerns. Main side effect of HIF-PHI was diarrhea. CONCLUSION: HIF-PHI might represent a safe, and convenient alternative to ESA in non-dialysis dependent CKD patients with anemia.

Acute kidney injury on chronic kidney disease: from congestive heart failure to light chain deposition disease and cast nephropathy in multiple myeloma.

Acute on chronic renal failure is a common but notably broad diagnosis. We present a 64-year-old man with a history of diastolic heart failure and chronic kidney disease, admitted for an elevated creatinine. History and physical examination were suggestive of decompensated heart failure; however, the careful interpretation of urinalysis rendered the diagnosis of multiple myeloma. On renal biopsy, the patient was found to have light chain deposition disease with cast nephropathy. Combination lesions in multiple myeloma are rare and require diligent histopathology for detection, including light microscopy, immunofluorescence and electron microscopy. These patients portray different demographics, renal manifestations, oncologic characteristics and outcomes, and hence, further studies isolating these combined lesions are warranted. Abbreviations: CKD: chronic kidney disease; CN: cast nephropathy; CT: computerized tomography; EDD: electron-dense deposits; EM: electron microscopy; IF: immunofluorescence; FLC: free light chain; LC: light chain; LCDD: light chain deposition disease; MIDD: monoclonal immunoglobulin deposition disease; MM: multiple myeloma; LM: light microscopy; NGS: nodular glomerulosclerosis; κ: kappa; λ: lambda.