Introduction
bleeding, infectious, chronic kidney disease, metals, neoplasia, artery laceration, infection, chronic renal insult, nephropathy, embolism, Chronic kidney disease
RENAL, DISEASE PROGRESSION, VASODILATION, BLEEDING, NEOPLASIA, DISEASE, DISEASES, EMBOLISM, INFECTION, HYPERURICEMIA, NEPHROPATHY, THROMBOEMBOLISM, EVENTS, HYPERTENSION, CHRONIC KIDNEY DISEASE, COMPLICATIONS, BROWN
Chronic kidney disease of unknown cause (CKDu), formerly known as Mesoamerican nephropathy, is an aggressive variant of chronic kidney disease first described in individuals in the coastal regions of Central America, including Nicaragua.Multiple investigations in the etiology of CKDu have examined infectious causes, agricultural pesticides, and genetic mutations—yielding conflicting data. Most recently, heavy metals have been implicated.Management of CKDu in Nicaragua is primarily focused on slowing disease progression by monitoring patients for diet compliance; management of cardiac risks; avoidance of nephro-toxic medications; and management of hyperuricemia. No effective therapy exists to halt the structural and functional alterations in CKDu. This disease is associated with high rates of mortality in Central American countries as dialysis is often not available.Histopathologic findings suggest that an effective treatment would need to block the acute and chronic inflammatory/fibrotic events. The observation of ischemic changes in affected glomeruli, such as wrinkling, suggests the possibility of compromised renal perfusion. Therefore, therapeutic interventions that promote local vasodilation and angiogenesis could be beneficial, with a goal of repair and recovery of glomeruli and tubules.One such intervention could be stem cell therapy. Multipotent stem cells [now called mesenchymal stem/stromal cells (MSC)], originally found within the bone marrow, are capable of differentiating into various cell types, which raised the possibility that stromal cells could be used to treat multiple diseases.While early studies investigated the role of stem cells in kidney repair by giving bone marrow MSCs directly into the parenchyma of the kidney, one of the least complicated forms of cellular intervention is to administer adipose-derived MSCs (ADMSC) via renal artery infusion. Renal artery perfusion has been shown to be an excellent method for delivering stems cells to aid kidney repair in experimental models.One method to obtain ADMSC at point of care and perform a same day cell infusion is through the use of liposuction, followed by collagenase treatment and washing of the lipoaspirate. The resulting cell mixture is called stromal vascular fraction (SVF) and contains numerous therapeutically-active cellular components. Brown et al. have analyzed SVF composition using cell lineage markers and fluorescence-activated cell sorting (FACS) and have documented the presence of ADMSCs, pericytes, endothelial cells, adipose and hematopoietic progenitors, and monocytes.The purpose of this first-in-human, open-label study was to determine feasibility and safety, and to gain potential evidence of clinical utility, of a single infusion of autologous SVF cells administered via renal artery catheterization in patients with stages 3-5 CKDu. The issues of feasibility for this trial included the ability to identify suitable patients, the willingness of patients to participate in a clinical trial, and the ability of patients to make all the required visits. The CKDu-affected population in Nicaragua tends to a physical-labor, rural working-class socio-economic background. Nicaragua is a small country of 6.5 millions with a centralized public medical system and a limited research capability; therefore, for purposes of this study, “feasibility” included the ability to collect all the required data. Critical issues for safety included complications from the invasive procedures of lipoaspiration and intrarenal artery perfusion (infection, bleeding, artery laceration, infection, bleeding, thromboembolism), and/or complications of the SVF cells (embolism, infection, acute or chronic renal insult, hypertension, neoplasia). Potential post-treatment efficacy was evaluated in terms of changes in vascular flow and renal function as outlined in Methods.We report herein the 36-month follow-up of 18 CKDu patients (36 kidneys) treated with SVF with regard to feasibility, safety, and potential clinical utility.