The Association of Urolithiasis with Uricosuria, Uricemia and their Combination.

BACKGROUND: There are conflicting data on the significance of hyperuricemia or hyperuricosuria in urolithiasis formation and on the need for medical treatment. OBJECTIVES: To assess the significance of hyperuricemia or hyperuricosuria in urolithiasis formation, particularly when hyperuricemia occurs with normal uricosuria. METHODS: The electronic medical records of patients treated in Haifa and the Western Galilee district of Clalit Health Services, Israel, were retrospectively screened for diagnosis of nephrolithiasis or renal or urinary tract/bladder calculi between February 2014 and April 2019. The diagnosis was confirmed by ultrasonography or computed tomography. The study group included patients with one of these diagnoses. Patients in the control group did not have these diagnoses. The inclusion criterion for all patients was the presence of both serum and urinary uric acid levels. RESULTS: The study group included 359 patients and the control group 267. After adjustment by logistic regression, we found no significant differences in the prevalence of hyperuricosuria in the study group (14.8%) compared to the control group (9.7%), odds ratio (OR) 1.54 (95% confidence interval [95%CI] 0.74-3.2, P = 0.245). No significant differences between the groups were observed for hyperuricemia prevalence (45.4% vs. 55.1%, respectively, OR 0.82, 95%CI 0.54-1.25, P = 0.355), nor among those without hyperuricosuria (OR 0.83, 95%CI 0.52-1.33, P = 0.438) and after propensity score matching (OR 0.93, 95%CI 0.66-1.3, P = 0.655). CONCLUSIONS: There were no significant differences in hyperuricemia or hyperuricosuria between the two groups of patients or in hyperuricemia among participants without hyperuricosuria.

Genetic Markers Among the Israeli Druze Minority Population With End-Stage Kidney Disease.

RATIONALE & OBJECTIVE: Genetic etiologies have been identified among approximately 10% of adults with chronic kidney disease (CKD). However, data are lacking regarding the prevalence of monogenic etiologies especially among members of minority groups. This study characterized the genetic markers among members of an Israeli minority group with end-stage kidney disease (ESKD). STUDY DESIGN: A national-multicenter cross-sectional study of Israeli Druze patients (an Arabic-speaking Near-Eastern transnational population isolate) who are receiving maintenance dialysis for ESKD. All study participants underwent exome sequencing. SETTING & PARTICIPANTS: We recruited 94 adults with ESKD, comprising 97% of the total 97 Druze individuals throughout Israel being treated with dialysis during the study period. PREDICTORS: Demographics and clinical characteristics of kidney disease. OUTCOME: Genetic markers. ANALYTICAL APPROACH: Whole-exome sequencing and the relationship of markers to clinical phenotypes. RESULTS: We identified genetic etiologies in 17 of 94 participants (18%). None had a previous molecular diagnosis. A novel, population-specific, WDR19 homozygous pathogenic variant (p.Cys293Tyr) was the most common genetic finding. Other monogenic etiologies included PKD1, PKD2, type IV collagen mutations, and monogenic forms of noncommunicable diseases. The pre-exome clinical diagnosis corresponded to the final molecular diagnosis in fewer than half of the participants. LIMITATIONS: This study was limited to Druze individuals, so its generalizability may be limited. CONCLUSIONS: Exome sequencing identified a genetic diagnosis in approximately 18% of Druze individuals with ESKD. These results support conducting genetic analyses in minority populations with high rates of CKD and for whom phenotypic disease specificity may be low. PLAIN-LANGUAGE SUMMARY: Chronic kidney disease (CKD) affects many people worldwide and has multiple genetic causes. However, there is limited information on the prevalence of genetic etiologies, especially among minority populations. Our national-multicenter study focused on Israeli Druze patients. Using exome-sequencing, we identified previously undetected genetic causes in nearly 20% of patients, including a new and population-specific WDR19 homozygous pathogenic variant. This mutation has not been previously described; it is extremely rare globally but is common among the Druze, which highlights the importance of studying minority populations with high rates of CKD. Our findings provide insights into the genetic basis of end-stage kidney disease in the Israeli Druze, expand the WDR19 phenotypic spectrum, and emphasize the potential value of genetic testing in such populations.

The ideal position of the peritoneal dialysis catheter is not always ideal.

PURPOSE: Peritoneal catheter dysfunction is a frequent complication of peritoneal dialysis (PD). Traditionally, dysfunction has been attributed to catheter malposition, but whether the location of the catheter tip in the small pelvis really determines proper function is unclear. METHODS: We reviewed 900 abdominal X-ray images of PD patients from a 7-year period in two PD units that use different catheter types (straight and Swan Neck Curled). RESULTS: In 52% of the images, the dialysis catheter tip was located in the ideal position in the small pelvis and in 48% in other sites. Peritoneal catheter function was normal at the time of imaging in 87% of those with ideal catheter tip position, and in 74% of those with other than ideal position. The tip was located in small pelvis in 35% of images performed during catheter dysfunction and in 56% of those performed during normal catheter function. There were no differences between two catheter types. The positive predictive value of abdominal X-ray images to predict catheter function was 26%, and the negative predictive value 87%. We also found a significant positive correlation between polycystic kidney disease and normal catheter function. In contrast, obese patients were more likely to have catheter malfunction. Previous abdominal surgery was not associated with catheter dysfunction. CONCLUSION: Our data showed a higher probability of normal function of peritoneal catheters whose tips were located in the small pelvis. However, also malpositioned catheters generally functioned well, and malpositioning of the PD catheter did not in itself explain its malfunction.

Neutrophil gelatinase-associated lipocalin in a triphasic rat model of adenine-induced kidney injury.

The aim of this study is to investigate whether NGAL, given its advantages over traditional biomarkers, can be used to describe the dynamic characteristics of the renal tubulointerstitial insult caused by adenine. Subsequently, it will be possible to assess NGAL as a biomarker of any acute kidney injury, on top of chronic interstitial disease, if NGAL levels are stable through the chronic phase of our adenine model. Study group rats were fed an adenine diet, and control group rats were fed a regular diet only. Blood and urine samples for urea, creatinine and NGAL were drawn from each rat at the beginning of the study and after 1, 3, 4, 5, 6, 7 and 8 weeks. Kidney slices from these rats were stained with Hematoxylin-eosin (HE) and ß-actin stainings. Serum urea, creatinine and NGAL levels and urinary NGAL/creatinine ratio in the study group were higher than baseline and than in the control group; these differences were statistically significant in some of the intervals. Tubulointerstitial changes and adenine crystals were evident in the study group rats. In the rats fed adenine, serum urea, creatinine and NGAL levels and urinary NGAL/creatinine ratio followed a triphasic pattern of kidney injury: an acute phase while on the adenine diet, a partial recovery phase after switching to the regular diet and a chronic kidney disease phase after stabilization of renal function. NGAL can serve a biomarker for acute kidney injury and possibly for chronic kidney disease in the tubulointerstitial rat model.

Phosphodiesterase-5 inhibition attenuates early renal ischemia-reperfusion-induced acute kidney injury: assessment by quantitative measurement of urinary NGAL and KIM-1.

Acute kidney injury (AKI) is a common clinical problem that still lacks effective treatment. Phosphodiesterase-5 (PDE5) inhibitors possess anti-apoptotic and anti-oxidant properties, making it a promising therapy for ischemia-reperfusion (I/R) injury of various organs. The present study evaluated the early nephroprotective effects of Tadalafil, a PDE5 inhibitor, in an experimental model of renal I/R. Sprague-Dawley rats were divided into two groups: vehicle-treated I/R (n = 10), and Tadalafil (10 mg/kg po)-treated I/R group (n = 11). After removal of the right kidney and collection of two baseline urine samples, the left renal artery was clamped for 45 min followed by reperfusion for 60, 120, 180, and 240 min. Functional and histological parameters of the kidneys from the various groups were determined. In the vehicle-treated I/R group, glomerular filtration rate was significantly reduced compared with that in normal kidneys. In addition, the ischemic kidney showed remarkable cast formation, necrosis, and congestion, a consistent pattern of acute tubular necrosis. Furthermore, urinary excretion of NGAL and KIM-1, two novel biomarkers of kidney injury, substantially increased following I/R insult. In contrast, Tadalafil treatment resulted in a significant improvement in kidney function and amelioration of the adverse histological alterations of the ischemic kidney. Noteworthy, the urinary excretion of NGAL and KIM-1 markedly decreased in the Tadalafil-treated I/R group. These findings demonstrate that Tadalafil possesses early nephroprotective effects in rat kidneys subjected to I/R insult. This approach may suggest a prophylactic therapy for patients with ischemic AKI.

Urinary NGAL and KIM-1: biomarkers for assessment of acute ischemic kidney injury following nephron sparing surgery.

PURPOSE: Nephron sparing surgery is considered the treatment of choice in most patients with confined renal cancer. Interrupting renal blood flow is often necessary during such surgery, which can induce significant renal injury. We explored the possibility of using urinary NGAL and KIM-1 excretion as novel biomarkers to assess the extent of acute kidney injury after nephron sparing surgery. MATERIALS AND METHODS: The study group included 27 patients who underwent open nephron sparing surgery for enhancing solid renal tumors. During surgery the renal artery was clamped for between 6 and 47 minutes. Urine samples were collected before surgery, and 1, 3, 8, 24, 48 and 72 hours after renal pedicle clamp removal. Urinary levels of NGAL and KIM-1 were determined. RESULTS: Renal artery clamping induced renal injury, as reflected by increased urinary NGAL and KIM-1 in all participants. These increases in urinary NGAL excretion were evident after 1 hour of renal ischemia and lasted for 72 hours. Urinary NGAL correlated with the serum creatinine increase and ischemia duration. Compared with patients without significantly increased serum creatinine, those with significantly increased serum creatinine after nephron sparing surgery had a greater increase in urinary NGAL but not in KIM-1. CONCLUSIONS: Renal injury severity after nephron sparing surgery could be quantitatively assessed by measuring urinary NGAL and KIM-1.

Acute effects of peritoneal dialysis solutions in the mesenteric microcirculation.

Long-term peritoneal dialysis induces morphological changes that may lead to gradual functional impairment of the peritoneal membrane. These changes are characterized by progressive reduction in solute transport or ultrafiltration failure. The mechanism of the peritoneal response to dialysis fluids has not yet been fully elucidated. We used video-microscopy for in vivo evaluation of microhemodynamics and peritoneal microvascular inflammatory response, after a single intraperitoneal exposure of rats to commercial PD fluids: (1) glucose 1.5 % PD solution; (2) lactate buffered glucose 4.25% PD solution; (3) Icodextrin 7%; (4) bicarbonate buffered glucose 3.86% PD fluid; and 5) Hanks solution. Sham-control groups were not injected. A 5-h exposure of the peritoneal membrane to glucose 1.5% PD solution or to Hanks solution did not induce a significant change in leukocyte rolling and adhesion. In contrast, PD solutions containing glucose 4.25% or Icodextrin 7.5% caused a significant 2-3-fold increase in leukocyte rolling (P < 0.001) and adhesion (P < 0.001) and a significant increase in venular blood flow velocity (P < 0.01) and shear rates (P < 0.05 for glucose 4.25%, and P < 0.01 for Icodextrin). Exposure to glucose 3.86% bicarbonate buffered (Physioneal) solution was associated with the lowest values of leukocyte rolling and adhesion among the PD solutions and with extremely higher venular flow velocities and shear rates. A single exposure to conventional PD solutions with a high concentration of glucose (4.25%) or polyglucose (Icodextrin 7.5%) induces changes consistent with an early peritoneal inflammatory response that may be attenuated by the use of bicarbonate-based fluids.

Peritoneal transport after long-term exposure to Icodextrin in rats.

BACKGROUND: Icodextrin, an effective osmotic substance that has been proposed as an alternative agent for peritoneal dialysis induces ultrafiltration over long dwells. This study examines the peritoneal transport after exposure to Icodextrin in rats. METHODS: Animals were divided in 4 groups and injected daily for 30 days with Icodextrin 7.5 % (n = 14), Glucose 4.25 % (n = 19) or glucose 4.25% plus Icodextrin 7.5 % (n = 13). Rats of the control group (n = 15) were not exposed. A 4-hour permeability study was performed using glucose at days 1, 30 and 60. At days 2, 31 and 61 the same animals were injected with Icodextrin. RESULTS: Slopes of effluent sodium at day 30 were significantly higher (p < 0.001) in the glucose (0.006 +/- 0.016), Icodextrin (0.013 +/- 0.014) and mixed groups (0.012 +/- 0.017) than in the control group (-0.041 +/- 0.021). Urea D/P ratio was not significantly different in the 4 groups. After 30 days, glucose effluent levels were significantly lower (p < 0.001) in the glucose (701 +/- 278 mg/dl), Icodextrin (552 +/- 209 mg/dl) and mixed groups (587 +/- 344 mg/dl) than in control rats (1519 +/- 413 mg/dl). Effluent protein (mg/l) in the mixed group (1,555 +/- 357) was significantly higher (p < 0.001) than control (376 +/- 33), glucose (1,015 +/- 232) and Icodextrin (765 +/- 75) groups at day 30. CONCLUSION: The long-term use of Icodextrin does not affect small molecule transport, but induces changes in the peritoneal protein excretion, especially when Icodextrin and glucose are injected together.