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Noninvasive monitoring of chronic kidney disease using pH and perfusion imaging.

ABSTRACT: Chronic Kidney Disease (CKD) is a cardinal feature of methylmalonic acidemia (MMA), a prototypic organic acidemia. Impaired growth, low activity, and protein restriction affect muscle mass and lower serum creatinine, which can delay diagnosis and management of renal disease. We have designed an alternative strategy for monitoring renal function based on administration of a pH sensitive MRI agent and assessed this in a mouse model. This protocol produced three metrics: kidney contrast, ~4% for severe renal disease mice compared to ~13% and ~25% for moderate renal disease and healthy controls, filtration fraction (FF), ~15% for severe renal disease mice compared to ~79% and 100% for moderate renal disease and healthy controls, and variation in pH, ~0.45 units for severe disease mice compared to 0.06 and 0.01 for moderate disease and healthy controls. Our results demonstrate that MRI can be used for early detection and monitoring of CKD.

SUBMITTER: Pavuluri K

PROVIDER: S-EPMC6693904 | biostudies-other | 2019 Aug

REPOSITORIES: biostudies-other

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Noninvasive monitoring of chronic kidney disease using pH and perfusion imaging.

Pavuluri KowsalyaDevi K Manoli Irini I Pass Alexandra A Li Yuguo Y Vernon Hilary J HJ Venditti Charles P CP McMahon Michael T MT

Science advances 20190814 8

Chronic Kidney Disease (CKD) is a cardinal feature of methylmalonic acidemia (MMA), a prototypic organic acidemia. Impaired growth, low activity, and protein restriction affect muscle mass and lower serum creatinine, which can delay diagnosis and management of renal disease. We have designed an alternative strategy for monitoring renal function based on administration of a pH sensitive MRI agent and assessed this in a mouse model. This protocol produced three metrics: kidney contrast, ~4% for se ...[more]

PMID: 31453331

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Project description:Patients with chronic kidney disease (CKD) are at an alarming risk of cardiovascular disease and fracture-associated mortality. CKD has been shown to have negative effects on vascular reactivity and organ perfusion. Although alterations in bone blood flow are linked to dysregulation of bone remodeling and mass in multiple conditions, changes to skeletal perfusion in the setting of CKD have not been explored. The goal of this study was to establish the effect of CKD on skeletal perfusion in a rat model of CKD. In two experiments with endpoints at 30 and 35 weeks of age, respectively, normal (NL) and Cy/+ (CKD) animals (n = 6/group) underwent in vivo intra-cardiac fluorescent microsphere injection to assess bone tissue perfusion. These two separate time points aimed to describe skeletal perfusion at 30 and 35 weeks based on previous studies demonstrating significant progression of hyperparthyroid bone disease during this timeframe. CKD animals had blood urea nitrogen (BUN) levels significantly higher than NL at both 30 and 35 weeks. At 30 weeks, perfusion was significantly higher in the femoral cortex (+259%, p < 0.05) but not in the tibial cortex (+140%, p = 0.11) of CKD animals relative to NL littermates. Isolated tibial marrow perfusion at 30 weeks showed a trend toward being higher (+183%, p = 0.08) in CKD. At 35 weeks, perfusion was significantly higher in both the femoral cortex (+173%, p < 0.05) and the tibial cortex (+241%, p < 0.05) in CKD animals when compared to their normal littermates. Isolated tibial marrow perfusion (-57%, p <0.05) and vertebral body perfusion (-71%, p <0.05) were lower in CKD animals. The current study demonstrates two novel findings regarding bone perfusion in an animal model of high turnover CKD. First, cortical bone perfusion in CKD animals is higher than in normal animals. Second, alterations in bone marrow perfision differed among the stages of CKD and were distinct from perfusion to the cortical bone. Determining whether these changes in bone perfusion are drivers, propagators, or consequences of skeletal deterioration in CKD will necessitate further work.

Project description:IntroductionAcute early vascular complications are rare, but serious complications after kidney transplantation. They often result in graft loss. For this reason, shortening the diagnostic process is crucial. Currently, it is standard procedure to monitor renal graft perfusion using Doppler ultrasound (DU). With respect to acute vascular complications, the main disadvantage of this type of examination is its periodicity. It would be of great benefit if graft blood perfusion could be monitored continuously during the early postoperative period. It appears evident that a well-designed near infrared spectroscopy (NIRS) monitoring system could prove very useful during the early post-transplantation period. Its role in the immediate diagnosis of vascular complications could result in a significant increase in graft salvage, thus improving the patient's overall quality of life and lowering morbidity and mortality for renal graft recipients. The aim of this study was to design, construct and test such a monitoring system.Materials and methodsWe designed a rough NIRS-based system prototype and prepared a two-stage laboratory experiment based on a laboratory pig model. In the first stage, a total of 10 animals were used to verify and optimize the technical aspects and functionality of the prototype sensor by testing it on the animal kidneys in-vivo. As a result of these tests, a more specific prototype was designed. During the second stage, we prepared a unique laboratory model of a pig kidney autotransplantation and tested the system for long-term functionality on a group of 20 animals. Overall sensitivity and specificity were calculated, and a final prototype was prepared and completed with its own analytic software and chassis.ResultsWe designed and constructed a NIRS-based system for kidney graft perfusion monitoring. The measurement system provided reliable performance and 100% sensitivity when detecting acute diminished blood perfusion of the transplanted kidneys in laboratory conditions.ConclusionThe system appears to be a useful tool for diagnosing diminished blood perfusion of kidney transplants during the early postoperative period. However, further testing is still required. We believe that applying our method in current human transplantation medicine is feasible, and we are confident that our prototype is ready for human testing.

Dataset Information

Noninvasive monitoring of chronic kidney disease using pH and perfusion imaging.

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Noninvasive monitoring of chronic kidney disease using pH and perfusion imaging.

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