Infiltrating cells play an important role in both the development of and recovery from acute kidney injury (AKI). Macrophages and renal dendritic cells are of particular interest because they can ...exhibit distinctly different functional phenotypes, broadly characterized as proinflammatory (M1) or tissue reparative (M2). Resident renal macrophages and dendritic cells participate in recovery from AKI in response to either ischemia/reperfusion or a model of selective proximal tubule injury induced by diphtheria-toxin-induced apoptosis in transgenic mice expressing the human diphtheria toxin receptor on proximal tubule cells. Colony-stimulating factor-1 (CSF-1) is an important factor mediating the recovery from AKI, and CSF-1 can stimulate macrophage and dendritic cell proliferation and polarization during the recovery phase of AKI. The kidney, and specifically the proximal tubule, is a major source of intrarenal CSF-1 production in response to AKI. We induced selective deletion of proximal tubule CSF-1 to determine its role in expansion and proliferation of renal macrophages and dendritic cells and in recovery from AKI. In both models of AKI, there was decreased M2 polarization, delayed functional and structural recovery, and increased tubulointerstitial fibrosis. Thus, intrarenal CSF-1 is an important mediator of macrophage/dendritic cell polarization and recovery from AKI.
Hypokalemia is a relatively common electrolyte disorder usually resulting from gastrointestinal wasting. Transient hyperkalemia in those treated for hypokalemia has been previously described to occur ...in 16% of hospitalized patients. The majority of those patients had acute, hospital-acquired hypokalemia. Here, we report a case of a young man with alcohol use disorder and chronic hypokalemia who was hospitalized for muscle weakness, abdominal pain, and intractable emesis. His potassium was 2.5 mEq/L on the day of admission. Four days later, with a creatinine at baseline (0.9 mg/dL), potassium abruptly increased to 6.7 mEq/L. He did not have evidence of hyperaldosteronism. In cases of chronic hypokalemia, we propose that the adaptive mechanisms of the distal tubule with total body potassium deficits require time to revert back to a nonactive state and that transient hyperkalemia may be observed during these “refractory” periods during which potassium supplementation is continued. The time required for disassembly of with no lysine kinases following resolution of hypokalemia is unknown. Hyperkalemia is an important consideration when treating patients with chronic hypokalemia.
The primary hyperoxalurias (PHs) are a group of diseases characterized by kidney stones, nephrocalcinosis, and chronic kidney disease. At stages of advanced kidney disease, glomerular filtration of ...oxalate becomes insufficient, plasma levels increase, and tissue deposition may occur. Hemodialysis is often unable to overcome the excess hepatic oxalate production. The current surgical management of primary hyperoxaluria type 1 (PH1) is combined liver kidney transplantation. In a subset of PH1 patients who respond to pyridoxine, kidney-only transplantation has been successfully performed. Recently, kidney-only transplantation has also been performed in PH1 patients receiving a small interfering RNA therapy called lumasiran. This drug targets the hepatic overproduction of oxalate, making kidney-only transplantation a potentially practical novel approach for managing PH1 patients with advanced kidney disease. It is unknown if similar effects could be seen with a different small interfering RNA agent called nedosiran. This article will briefly review PH1, describe the small interfering RNA therapies being used to treat PH, summarize the reported cases of kidney-only transplantation performed with lumasiran, and detail a case of kidney-only transplantation performed in a PH1 patient receiving nedosiran.
The primary hyperoxalurias (PHs) are a group of diseases characterized by kidney stones, nephrocalcinosis, and chronic kidney disease. At stages of advanced kidney disease, glomerular filtration of ...oxalate becomes insufficient, plasma levels increase, and tissue deposition may occur. Hemodialysis is often unable to overcome the excess hepatic oxalate production. The current surgical management of primary hyperoxaluria type 1 (PH1) is combined liver kidney transplantation. In a subset of PH1 patients who respond to pyridoxine, kidney-only transplantation has been successfully performed. Recently, kidney-only transplantation has also been performed in PH1 patients receiving a small interfering RNA therapy called lumasiran. This drug targets the hepatic overproduction of oxalate, making kidney-only transplantation a potentially practical novel approach for managing PH1 patients with advanced kidney disease. It is unknown if similar effects could be seen with a different small interfering RNA agent called nedosiran. This article will briefly review PH1, describe the small interfering RNA therapies being used to treat PH, summarize the reported cases of kidney-only transplantation performed with lumasiran, and detail a case of kidney-only transplantation performed in a PH1 patient receiving nedosiran.
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