Global Kidney Function Research Articles

Physiological aspects of pig kidney xenotransplantation and implications for management following transplant.

Successful organ transplantation between species is now possible, using genetic modifications. This article aims to provide a comprehensive overview of the differences and similarities in kidney function between humans, primates, and pigs, in preparation for pig-allograft to human xenotransplantation. The kidney, as the principal defender of body homeostasis, acts as a sensor, effector, and regulator of physiologic feedback systems. Considerations are made for anticipated effects on each system when a pig kidney is placed into a human recipient. Discussion topics include anatomy, global kidney function, sodium and water handling, kidney hormone production and response to circulating hormones, acid-base balance, and calcium and phosphorus handling. Based on available data, pig kidneys are anticipated to be compatible with human physiology, despite a few barriers.

Endoscopic treatment of ureterocele in children: Results of a single referral tertiary center over a 10 year-period

The management of UCs remain controversial, especially for UCs with duplex collecting systems that still represent a great challenge in paediatric urology. Several approaches have been used and a shared management is not yet validated. Aim of our study is to evaluate the results of the endoscopic treatment of UC comparing ortothopic single-system UC and ectopic duplex-system UC over a 10-year period in a single referral tertiary center. Success was defined as resolution of dilation, lack of urinary infections and preservation of renal function. We retrospectively reviewed medical records of children with a diagnosis of UC who underwent endoscopic puncture at our division from January 2009 to January 2019. Patients were divided in two groups: Group A composed of patients with ectopic UC associated with renal duplex system and Group B with orthotopic UC in single collecting system. We identified 48 paediatric patients treated with transurethral primary endoscopic incision. Groups result homogeneous for clinical and pathological characteristics. The only statistical significative difference between the two samples was the age at diagnosis (p value with Yates correction=0.01). We considered as a therapeutic success infections control and the elimination of obstruction with preservation of global kidney function. Based on that, our success rate after single (77%) or double (92%) endoscopic treatment is higher than data reported in literature. Differently from previous studies, vescico-ureteral reflux without UTIs was not considered as a failure of the procedure. The present study has some limitations: it is a retrospective and monocentric serie and it lacked a longer follow-up; on the other hand, it has been conducted on a quite large sample size and it is one of the few studies that compares the endoscopic treatment between orthotopic and ectopic UC. Our data report primary endoscopic puncture of ureterocele as a simple, effective, and safe procedure also in long-term follow up. This technique avoids the need for additional surgery in the majority of the patients, also in the case of an ectopic UC associated to a duplex system.

P0513NECROINFLAMMATION VERSUS CRYSTAL CLOTS AS THERAPEUTIC TARGET IN CHOLESTEROL CRYSTAL EMBOLISM-RELATED KIDNEY INFARCT

Abstract Background and Aims Cholesterol crystal embolism (CCE) is usually a consequence of the rupture of atheromatous plaques in patients with advanced atherosclerosis. We hypothesized that necroinflammation contributes to CCE-related kidney injury/disease (AKI/AKD). Method Injection of cholesterol crystal (CC) into C56BL/6 WT mice kidney via the left kidney artery induced vascular obstruction, kidney infarction, and GFR loss (measured by transcutaneous monitoring of sinistrin clearance in awake and unrestricted mice). GFR recovered to baseline at 2 weeks despite persistent kidney injury and scarring, probably because the non-injected right kidney developed compensatory hypertrophy. To study the role of necroinflammation in this process, we injected CC to either Mlkl-/- mice or WT mice pre-treated with PBS, the necroptosis inhibitor Nec-1s or the NLRP3 inhibitor MCC950 30 min before CC injection. Results At 24h, Nec-1s, MCC950 treatment had significantly reduced infarct size, kidney injury, neutrophil infiltration, and vascular injury compared to PBS control group. Reduced infarct size, e.g. with Nec-1s persistented until day 14. CC injection into Mlkl-/- mice gave the same results. However, none of these interventions had an effect on GFR loss, i.e. AKI because they did not affect crystal clot formation in the arteria afferent to glomerular perfusion. In contrast, anticoagulant treatment prevented infarcts and GFR loss. Conclusion In this new model of unilateral CCE-induced AKI/AKD global kidney function recovers within 14 d, presumably due to adaptive responses in the contralateral kidney as the post-infarct tissue injury persists and leads to kidney atrophy. As both the NLRP3 inflammasome as well as necroptosis are involved in kidney infarct formation, we conclude on necroinflammation as the central mechanism of CCE-induced AKI/AKD. However, what defines AKI is renal function. We found that crystal clot formation is upstream of kidney infarction but independent of necroinflammation. We conclude, despite necroinflammation is central in kidney infarct formation, crystal clots are the better therapeutic target to prevent CCE-related AKI.

MP41-09 ASSESSMENT OF SURGICAL OUTCOMES OF THE NON-RENORRHAPHY TECHNIQUE IN OPEN PARTIAL NEPHRECTOMY FOR =T1B RENAL TUMORS

You have accessJournal of UrologyKidney Cancer: Localized: Surgical Therapy I1 Apr 2016MP41-09 ASSESSMENT OF SURGICAL OUTCOMES OF THE NON-RENORRHAPHY TECHNIQUE IN OPEN PARTIAL NEPHRECTOMY FOR =T1B RENAL TUMORS Toshio Takagi, Tsunenori Kondo, Kenji Omae, Junpei Iizuka, Hirohito Kobayashi, Yasunobu Hashimoto, and Kazunari Tanabe Toshio TakagiToshio Takagi More articles by this author , Tsunenori KondoTsunenori Kondo More articles by this author , Kenji OmaeKenji Omae More articles by this author , Junpei IizukaJunpei Iizuka More articles by this author , Hirohito KobayashiHirohito Kobayashi More articles by this author , Yasunobu HashimotoYasunobu Hashimoto More articles by this author , and Kazunari TanabeKazunari Tanabe More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.176AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Renorrhaphy technique is a standard method to adapt renal parenchyma in partial nephrectomy (PN). However, adapting the renal parenchyma into a suitable shape without damaging vessels in cases of large renal tumors located at the renal hilum can be challenging, which has potential to reduce vascularized parenchymal mass. We assessed surgical outcomes between the non-renorrhaphy and renorrhaphy techniques in open partial nephrectomy for ≥ T1b renal tumors using volumetric studies. METHODS We retrospectively analyzed the records of 91 patients with normal contralateral kidneys who underwent both open PN for ≥T1b renal tumors and pre- and postoperative enhanced computed tomography between 2010 and 2014. Volumetric studies to assess vascularized parenchymal volume of the operated kidney were performed within 2 months preoperatively and 6 months postoperatively. Using the non-renorrhaphy technique, hemorrhagic areas on the surface of the renal parenchyma were coagulated by using monopolar soft-coagulation, while a TachoSil® tissue-sealing sheet was placed on the resected bed. RESULTS A total of 50 patients underwent renorrhaphy and 41 patients underwent non-renorrhaphy. Patient backgrounds and R.E.N.A.L Nephrometry scores were not significantly different between the two groups. Cold ischemia time was significantly longer in the renorrhaphy than in the non-renorrhaphy (52min vs. 42min, p=0.0162). However, significant differences were not observed in the preservation rate of the vascularized parenchymal mass in the operated kidney (renorrhaphy,71%:non-renorrhaphy,70%, p=0.5054) and global kidney function (renorrhaphy,88%: non-renorrhaphy,90%, p=0.3653) between the two groups. Age is the only predictor for global kidney function preservation (table). Renal artery pseudoaneurysm occurred in two cases in both groups. Urinary fistula tended to occur more frequently in non-renorrhaphy (2 cases) than in renorrhaphy (5 cases), though this difference was not statistically significant (p=0.237). CONCLUSIONS The non-renorrhaphy technique failed to show a benefit in the preservation of vascularized parenchymal mass of the operated kidney and global renal function for ≥T1b renal tumors compared to the renorrhaphy technique. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e563 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Toshio Takagi More articles by this author Tsunenori Kondo More articles by this author Kenji Omae More articles by this author Junpei Iizuka More articles by this author Hirohito Kobayashi More articles by this author Yasunobu Hashimoto More articles by this author Kazunari Tanabe More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Assessment of Surgical Outcomes of the Non-renorrhaphy Technique in Open Partial Nephrectomy for ≥T1b Renal Tumors

To assess surgical outcomes between the non-renorrhaphy and renorrhaphy techniques in open partial nephrectomy for ≥T1b renal tumors using volumetric studies. We retrospectively analyzed the records of 91 patients with normal contralateral kidneys who underwent both open partial nephrectomy for ≥T1b renal tumors and pre- and postoperative enhanced computed tomography between 2010 and 2014. Volumetric studies to assess vascularized parenchymal volume of the operated kidney were performed within 2 months preoperatively and 6 months postoperatively. Using the non-renorrhaphy technique, we coagulated hemorrhagic areas on the surface of the renal parenchyma by monopolar soft coagulation, while a TachoSil tissue-sealing sheet was placed on the resected bed. A total of 50 patients underwent renorrhaphy and 41 patients underwent non-renorrhaphy. Patient backgrounds and R.E.N.A.L. nephrometry scores were not significantly different between the two groups. Cold ischemia time was significantly longer in the renorrhaphy than that in the non-renorrhaphy (52 vs 42 minutes, P = .0162). However, significant differences were not observed in the preservation rate of the vascularized parenchymal mass in the operated kidney (renorrhaphy, 71%; non-renorrhaphy, 70%; P = .5054) and global kidney function (renorrhaphy, 88%; non-renorrhaphy, 90%; P = .3653) between the two groups. Renal artery pseudoaneurysm occurred in 2 cases in both groups. Urinary fistula tended to occur more frequently in non-renorrhaphy (2 cases) than in renorrhaphy (5 cases), though this difference was not statistically significant (P = .237). The non-renorrhaphy technique failed to show a benefit in the preservation of vascularized parenchymal mass of the operated kidney and global renal function for ≥T1b renal tumors compared to the renorrhaphy technique.

Does percutaneous nephrolithotomy and its outcomes have an impact on renal function? Quantitative analysis using SPECT-CT DMSA.

To assess the functional effects of percutaneous nephrolithotomy (PCNL) and its outcomes in the operated kidney, we prospectively studied 30 consecutive cases undergoing PCNL. Kidney function was evaluated preoperatively and 3 months after surgery with serum creatinine, glomerular filtration rate (GFR), and with (99m)Tc-DMSA SPECT-CT scans to determine the differential renal function (DRF). PCNL effects in the operated kidney DRF were considered globally (DRFPLANAR, DRFSPECT) and in the region of percutaneous access (DRFACCESS). PCNL functional impact was also assessed depending on its outcomes, namely success (stone-free status) and the development of perioperative complications. PCNL has rendered 73 % of the cases completely stone free with a 33 % complication rate. After PCNL, serum creatinine and GFR did not change significantly, whereas DRFPLANAR and DRFSPECT dropped 1.2 % (p = 0.014) and 1.0 % (p = 0.041), respectively. The highest decrease was observed in DRFACCESS (1.8 %, p = 0.012). Stone-free status after PCNL did not show any impact on kidney function. Conversely, cases that suffered from a complication showed impairment in serum creatinine (0.1 mg/dL, p = 0.028), in GFR (11.1 mL/min, p = 0.036) as well as in DRFPLANAR (2.7 %, p = 0.018), DRFSPECT (2.2 %, p = 0.023) and DRFACCESS (2.7 %, p = 0.049). We conclude that PCNL has a minimal impact on global kidney function, which is mainly located in the region of percutaneous access. The advent of perioperative complications increased PCNL functional damage, whereas the stone-free status did not show any meaningful effect.

Unilateral ureteral obstruction: beyond obstruction

Unilateral ureteral obstruction is a popular experimental model of renal injury. However, the study of the kidney response to urinary tract obstruction is only one of several advantages of this model. Unilateral ureteral obstruction causes subacute renal injury characterized by tubular cell injury, interstitial inflammation and fibrosis. For this reason, it serves as a model both of irreversible acute kidney injury and of events taking place during human chronic kidney disease. Being a unilateral disease, it is not useful to study changes in global kidney function, but has the advantage of a low mortality and the availability of an internal control (the non-obstructed kidney). Experimental unilateral ureteral obstruction has illustrated the molecular mechanisms of apoptosis, inflammation and fibrosis, all three key processes in kidney injury of any cause, thus providing information beyond obstruction. Recently this model has supported key concepts on the role in kidney fibrosis of epithelial-mesenchymal transition, tubular epithelial cell G2/M arrest, the anti-aging hormone Klotho and renal innervation. We now review the experimental model and its contribution to identifying novel therapeutic targets in kidney injury and fibrosis, independently of the noxa.

Tubular kidney function in patients with type 2 Diabetes mellitus, microalbuminuria and proteinuria

Diabetes mellitus (DM) and hypertension are the most frequent causes of kidney function damage. Many different tests are developed to detect reversible functional kidney changes (detection of microalbuminuria and selective urinary enzymes). The aim of our study was to examine tubular kidney function in type 2 DM patients with different proteinuria levels, and to compare these results with healthy people. The patients with type 2 DM and creatinine clearance >80 ml/min were included in the study. According to the levels of proteinuria, the patients were classified in three groups: group I--patients with proteinuria <300 mg/24 h, and no microalbuminuria; group II--the patients with proteinuria <300 mg/24 h and microalbuminuria >20 mg/24 h; and group III--the patients with proteinuria >300 mg/24 h. The control group consisted of healthy subjects. The study revealed that in type 2 DM patients and normal global kidney function, fractional excretions of sodium, potassium, and phosphates as well as renal phosphate concentrations were not adequately sensitive markers to detect damage in tubular kidney function in DM. There were some changes of urate fractional excretion in these patients: this value was significantly lower in patients with microalbuminuria compared with those with proteinuria >300 mg/24 h, as well as in the control group (p < 0.05). Hormone dependent tubular kidney activity, urinary osmolarity, and urea fractional excretion in all patients were within normal ranges. It is evident that routine laboratory analyses are not sensitive markers to detect early changes of kidney function in type 2 DM.

Bladder exstrophy-epispadias complex: management and preliminary results

Retrospective evaluation of operative techniques and perioperative management as related to the primary anatomical and functional situation as well as analysis of the preliminary postoperative results regarding kidney function, continence and complications. From October 1992 to April 2003, 21 patients with bladder exstrophy-epispadias complex were treated, consisting of 12 children with untreated exstrophy and 9 who had undergone unsuccessful previous operations. Single-stage complete repair using the Erlangen concept was done during the first weeks of life in 8 infants and before school age in 3 children. One 13 year old girl had received a primary Mainz pouch II. The 9 unsuccessfully operated patients required a variety of different operations. The mean follow-up of 17 regularly controlled children was 62 months (range 3 to 129 months). In all children global kidney function remained stable, while reflux or obstruction was responsible for impaired unilateral split function ranging between 31 % and 45 % in 5. Four children were continent day and night after complete single-stage repair, 4 after ureterosigmoidostomy or Mainz pouch II and 5 after augmentation. In the newborn with previously untreated exstrophy-epispadias, we recommend single-stage complete functional reconstruction within the first weeks of life. Continence without loss of kidney function can be achieved in 50 % of these children. If adequate bladder capacity and continence cannot be achieved, an augmentation procedure or Mainz pouch II is our method of choice.

Renal nuclear medicine

The measurement of renal function has been a major field of interest in nuclear medicine. Many studies in the literature are still dedicated to this subject, with the aim of replacing the traditional urinary clearance methods with simpler and easier techniques. Simplified plasma clearance methods appear of sufficient accuracy to estimate global kidney function, except in very low function in which urinary clearance is still indicated. Gamma-camera methods have also been developed that, although of a lesser accuracy than the in vitro techniques, offer the important advantage of allowing renal imaging with the estimation of separate kidney function. Because of the intimate link between kidney function and structure, the diagnosis of nephrourological diseases has represented an important goal of nuclear medicine research. The functional information attainable with radionuclides is a valuable complement to the morphological information of imaging techniques such as x-ray computed tomography, ultrasonography, and magnetic resonance imaging. Recent contributions of nuclear medicine to the progress of clinical nephrology include the evaluation of renal function and the diagnostic work-up of renovascular hypertension, obstructive nephropathy, urinary tract infection, and renal transplantation.

Renal function after kidney transplantation in children. A comparison of conventional immunosuppression with cyclosporine.

Clearance studies were performed in 32 transplanted children treated with CsA in combination with low-dose prednisolone (CsA group), and the results were compared with those of 29 children transplanted earlier and treated with azathioprine and prednisolone (CIS group). Serum creatinine and urea levels 6 weeks and 1 year after transplantation (Tx) were significantly higher in the CsA than in the CIS group. Clearance studies 6 weeks after Tx exhibited significantly lower rates in the CsA group: Cin = 47 +/- 16.5 versus 83 +/- 25 ml/min/1.73 sqm, CPAH = 271 +/- 110 versus 503 +/- 181 ml/min/1.73 sqm (P less than 0.001). The filtration fractions were not different (19.1 versus 17.1%). The tubular phosphate reabsorption per ml GFR (Tp/Cin) was only slightly lower in the CsA group (0.76 +/- 0.23 mumol/ml versus 0.93 +/- 0.29; P = 0.09). The endogenous glucose clearance rates were equally elevated in both groups and returned to normal after 1 year. The creatinine clearance (Ccr) had dropped in both groups by a mean for 13 ml/min/1.73 sqm between 6 weeks and 1 year after Tx. No correlation was found between the Ccr and the CsA blood levels, but Ccr was inversely correlated with the number of rejection episodes (r = -0.72, P = 0.001). In conclusion, renal allografts in CsA-treated children exhibited a significantly lower function than in CIS-treated children. The effect was related to the global kidney function without any signs of additional tubular toxicity and was apparent within the first weeks after Tx. Thereafter, the decline in graft function was comparable in both groups and could not be related to CsA treatment.