Intraluminal measurement of papillary duct urine pH, in vivo: a pilot study in the swine kidney

We describe the in vivo use of an optic-chemo microsensor to measure intraluminal papillary duct urine pH in a large mammal. Fiber-optic pH microsensors have a tip diameter of 140-µm that allows insertion into papillary Bellini ducts to measure tubule urine proton concentration. Anesthetized adult pigs underwent percutaneous nephrolithotomy to access the lower pole of the urinary collecting system. A flexible nephroscope was advanced towards an upper pole papilla with the fiber-optic microsensor contained within the working channel. The microsensor was then carefully inserted into Bellini ducts to measure tubule urine pH in real time. We successfully recorded tubule urine pH values in five papillary ducts from three pigs (1 farm pig and 2 metabolic syndrome Ossabaw pigs). Our results demonstrate that optical microsensor technology can be used to measure intraluminal urine pH in real time in a living large mammal. This opens the possibility for application of this optical pH sensing technology in nephrolithiasis

Mechanism by which shock wave lithotripsy can promote formation of human calcium phosphate stones

Human stone calcium phosphate (CaP) content correlates with higher urine CaP supersaturation (SS) and urine pH as well as with the number of shock wave lithotripsy (SWL) treatments. SWL does damage medullary collecting ducts and vasa recta, sites for urine pH regulation. We tested the hypothesis that SWL raises urine pH and therefore Cap SS, resulting in CaP nucleation and tubular plugging. The left kidney (T) of nine farm pigs was treated with SWL, and metabolic studies were performed using bilateral ureteral catheters for up to 70 days post-SWL. Some animals were given an NH4Cl load to sort out effects on urine pH of CD injury vs. increased HCO3 (-) delivery. Histopathological studies were performed at the end of the functional studies. The mean pH of the T kidneys exceeded that of the control (C) kidneys by 0.18 units in 14 experiments on 9 pigs. Increased HCO3 (-) delivery to CD is at least partly responsible for the pH difference because NH4Cl acidosis abolished it. The T kidneys excreted more Na, K, HCO3 (-), water, Ca, Mg, and Cl than C kidneys. A single nephron site that could produce losses of all of these is the thick ascending limb. Extensive injury was noted in medullary thick ascending limbs and collecting ducts. Linear bands showing nephron loss and fibrosis were found in the cortex and extended into the medulla. Thus SWL produces tubule cell injury easily observed histopathologically that leads to functional disturbances across a wide range of electrolyte metabolism including higher than control urine pH

Preliminary Report on Stone Breakage and Lesion Size Produced by a New Extracorporeal Electrohydraulic (Sparker Array) Discharge Device

Objective To determine if an innovative extracorporeal electrohydraulic shock wave device (sparker array) can effectively fracture artificial stones in vitro and in vivo, and if sparker array treatment produces a renal lesion in our pig model of lithotripsy injury. Results of these experiments will be used to help evaluate the suitability of this device as a clinical lithotripter. Methods Utracal-30 artificial stones were placed in a holder at the focus of the sparker array and treated with 600 shock waves (21.6 kV, 60 shocks/min). Stone fragments were collected, dried and weighed to determine stone breakage. In vivo stone breakage entailed implanting stones into pigs. These stones were treated with 600 or 1200 shock waves and the fragments collected for analysis. Lesion analysis consisted of treating the left kidney of pigs with 1200 or 2400 shock waves and quantitating the hemorrhagic lesion. Results In vitro, 71±2% of each artificial stone was fractured to < 2 mm in size. In vivo stone breakage averaged 63%. Renal injury analysis revealed that only 1 out of 7 kidneys showed evidence of hemorrhagic injury in the treated area. Conclusions The sparker array consistently comminuted artificial stones demonstrating its ability to fracture stones like other lithotripters. Also, the sparker array caused little to no renal injury at the settings used in this study. These findings suggest further research is warranted to determine the potential of this device as a clinical lithotripter

Effect of renal shock wave lithotripsy on the development of metabolic syndrome in a juvenile swine model: a pilot study

PURPOSE: We performed a pilot study to assess whether renal shock wave lithotripsy influences metabolic syndrome onset and severity. MATERIALS AND METHODS: Three-month-old juvenile female Ossabaw miniature pigs were treated with shock wave lithotripsy (2,000 shock waves at 24 kV with 120 shock waves per minute in 2) or sham shock wave lithotripsy (no shock waves in 2). Shock waves were targeted to the upper pole of the left kidney to model treatment that would also expose the pancreatic tail to shock waves. Pigs were then instrumented to directly measure arterial blood pressure via an implanted radiotelemetry device. They later received a hypercaloric atherogenic diet for about 7 months. Metabolic syndrome development was assessed by the intravenous glucose tolerance test. RESULTS: Metabolic syndrome progression and severity were similar in the sham treated and lithotripsy groups. The only exception arterial blood pressure, which remained relatively constant in sham treated pigs but began to increase at about 2 months towards hypertensive levels in lithotripsy treated pigs. Metabolic data on the 2 groups were pooled to provide a more complete assessment of metabolic syndrome development and progression in this juvenile pig model. The intravenous glucose tolerance test revealed substantial insulin resistance with impaired glucose tolerance within 2 months on the hypercaloric atherogenic diet with signs of further metabolic impairment at 7 months. CONCLUSIONS: These preliminary results suggest that renal shock wave lithotripsy is not a risk factor for worsening glucose tolerance or diabetes mellitus onset. However, it appears to be a risk factor for early onset hypertension in metabolic syndrome

Development of a Novel Magnetic Resonance Imaging Acquisition and Analysis Workflow for the Quantification of Shock Wave Lithotripsy-Induced Renal Hemorrhagic Injury

Introduction The current accepted standard for quantifying shock wave lithotripsy (SWL)-induced tissue damage is based on morphometric detection of renal hemorrhage in serial tissue sections from fixed kidneys. This methodology is time and labor intensive and is tissue destructive. We have developed a non-destructive magnetic resonance imaging (MRI) method that permits rapid assessment of SWL-induced hemorrhagic lesion volumes in post-mortem kidneys using native tissue contrast to reduce cycle time. Methods Kidneys of anesthetized pigs were targeted with shock waves using the Dornier Compact S lithotripter. Harvested kidneys were then prepared for tissue injury quantification. T1 weighted (T1W) and T2 weighted (T2W) images were acquired on a Siemens 3T Tim Trio MRI scanner. Images were co-registered, normalized, difference (T1W–T2W) images generated, and volumes classified and segmented using a Multi-Spectral Neural Network (MSNN) classifier. Kidneys were then subjected to standard morphometric analysis for measurement of lesion volumes. Results Classifications of T1W, T2W and difference image volumes were correlated with morphometric measurements of whole kidney and parenchymal lesion volumes. From these relationships, a mathematical model was developed that allowed predictions of the morphological parenchymal lesion volume from MRI whole kidney lesion volumes. Predictions and morphology were highly correlated (R=0.9691, n=20) and described by the relationship y=0.84x+0.09, and highly accurate with a sum of squares difference error of 0.79%. Conclusions MRI and the MSNN classifier provide a semi-automated segmentation approach, which provide a rapid and reliable means to quantify renal injury lesion volumes due to SWL

Shock wave lithotripsy targeting of the kidney and pancreas does not increase the severity of metabolic syndrome in a porcine model

PURPOSE: We determined whether shock wave lithotripsy of the kidney of pigs with metabolic syndrome would worsen glucose tolerance or increase the risk of diabetes mellitus. MATERIALS AND METHODS: Nine-month-old female Ossabaw miniature pigs were fed a hypercaloric atherogenic diet to induce metabolic syndrome. At age 15 months the pigs were treated with 2,000 or 4,000 shock waves (24 kV at 120 shock waves per minute) using an unmodified HM3 lithotripter (Dornier MedTech, Kennesaw, Georgia). Shock waves were targeted to the left kidney upper pole calyx to model treatment that would also expose the pancreatic tail to shock waves. The intravenous glucose tolerance test was done in conscious fasting pigs before lithotripsy, and 1 and 2 months after lithotripsy with blood samples taken for glucose and insulin measurement. RESULTS: Pigs fed the hypercaloric atherogenic diet were obese, dyslipidemic, insulin resistant and glucose intolerant, consistent with metabolic syndrome. Assessments of insulin resistance, glucose tolerance and pancreatic β cell function from fasting plasma glucose and insulin levels, and the glucose and insulin response profile to the intravenous glucose tolerance test were similar before and after lithotripsy. CONCLUSIONS: The metabolic syndrome status of pigs treated with shock wave lithotripsy was unchanged 2 months after kidney treatment with 2,000 high amplitude shock waves or overtreatment with 4,000 high amplitude shock waves. These findings do not support a single shock wave lithotripsy treatment of the kidney as a risk factor for the onset of diabetes mellitus

In Vivo Renal Tubule pH in Stone Forming Human Kidneys

Introduction: There is evidence that patients with a history of ileostomies who make acidic urine and form uric acid or calcium oxalate stones may plug some collecting ducts with calcium phosphate (CaP) and urate crystals. This is a paradoxical finding as such minerals should not form at an acid pH. One possible explanation is the presence of acidification defects due to focal damage to inner medullary collecting duct and duct of Bellini (BD) cells. We sought to further investigate this hypothesis through direct measurement of ductal pH in dilated Bellini ducts in patients with ileostomies undergoing percutaneous nephrolithotomy for stone removal. Methods: After obtaining IRB approval, we used a fiber-optic pH microsensor with a 140 µm diameter tip to measure intraluminal pH from the bladder, saline irrigant and dilated BD’s of patients undergoing PCNL. Results: Measurements were taken from three patients meeting inclusion criteria. Measured pH of bladder urine ranged from 4.97 – 5.58 and pH of saline irrigant used during surgery ranged from 5.17 – 5.75. BD measurements were achieved in 11 different BDs. Mean intraductal BD pH was more than 1 unit higher than bulk urine (6.43 ± 0.22 vs. 5.31 ± 0.22, p<0.01). Conclusions: This is the first evidence for focal acidification defects within injured/dilated BD of human kidneys producing a highly acidic bulk phase urine. These results may help explain the paradoxical finding of CaP and urate plugs in dilated ducts of patients with stone forming diseases characterized by highly acidic urine

Intraluminal measurement of papillary duct urine pH, in vivo: a pilot study in the swine kidney

We describe the in vivo use of an optic-chemo microsensor to measure intraluminal papillary duct urine pH in a large mammal. Fiber-optic pH microsensors have a tip diameter of 140-µm that allows insertion into papillary Bellini ducts to measure tubule urine proton concentration. Anesthetized adult pigs underwent percutaneous nephrolithotomy to access the lower pole of the urinary collecting system. A flexible nephroscope was advanced towards an upper pole papilla with the fiber-optic microsensor contained within the working channel. The microsensor was then carefully inserted into Bellini ducts to measure tubule urine pH in real time. We successfully recorded tubule urine pH values in five papillary ducts from three pigs (1 farm pig and 2 metabolic syndrome Ossabaw pigs). Our results demonstrate that optical microsensor technology can be used to measure intraluminal urine pH in real time in a living large mammal. This opens the possibility for application of this optical pH sensing technology in nephrolithiasis